interactions and reaction mechansims in peroxidases and aldo-keto reductases Carme Rovira ICREA / Parc Científic de Barcelona Barcelona
|
|
- Gloria Caldwell
- 6 years ago
- Views:
Transcription
1 Molecular modeling of enzyme-substrate interactions and reaction mechansims in peroxidases and aldo-keto reductases Carme Rovira ICREA / Parc Científic de Barcelona Barcelona
2 What we do Molecular (atomistic) simulation Application of classical methodologies (based on Newton s equations) to investigate the properties of matter from an atomic or molecular basis. oxygen active center myoglobin
3 Techniques Classical molecular dynamics Interaction energy from MM E = E bond + E ang + E dih + E vdw + E elec + Ab initio molecular dynamics Interaction energy from QM E = min E ρ(r) [ ρ(r), { R }] I QM/MM CPMD QM MM computationally intense calculations Other: Docking, structure alignment, sequence alignment,...
4 Projects in MN Substrate recognition and catalysis in 1. Heme peroxidases and catalases N N (protection against oxidative damage) N N Fe O O - O O - heme 2. Aldo-keto reductases (reduction of carbonyl compounds) all trans retynaldehyde retynaldehyde
5 1. Heme peroxidases Oxidation of substrates using hydrogen peroxide H 2 O 2 + 2S red 2H 2 O + 2S ox (S red / S ox = reduced / oxidized substrate) His42 Role: Defense against pathogens His170 heme Applications: Biotechnology and biocatalysis Horseradish peroxidase (HRP) Berglund et al. Nature 2002 (PDB code 1h58)
6 Catalase-peroxidases (KatG) heme peroxidases Bifunctional enzyme peroxidase: H 2 O 2 + 2S red 2H 2 O + 2S ox catalase: 2 H 2 O 2 2 H 2 O + O 2 His Arg heme His Asp
7 KatG as antitubercular target heme peroxidases KATG is responsible for INH activation (Zhang et al. Nature , 591-3) KATG mutations cause drug resistance to INH (Altamirano et al. J. Infect. Dis , 162-5) First X-Ray structures ( ) Isoniazid (INH) Open questions How does the enzyme operate? Where does INH bind? INH activation mechanism?
8 Reaction intermediates heme peroxidases Compound I intermediate Tyr238-O - Tyr238-OH ph heme heme P. Vidossich et al. JACS 129, (2007). O + typical peroxidase intermediate Alfonso-Prieto et al. JACS 129, 4193 (2007).
9 Reaction intermediates heme peroxidases Compound I intermediate Tyr238-O - Tyr238-OH ph heme Trp330 heme P. Vidossich et al. JACS 129, (2007). Uncommon electronic structure (ph dependent) Possible relation with enzyme bifunctionality (peroxidase and catalase reactions occur at low/high ph)
10 Catalase reaction mechanism heme peroxidases ~ QM atoms 10 ps AIMD, 10 5 h MN (4 months, 64/128 procs). Reaction free energy landscape products path A path B reactants t Two different pathways (useful for catalase inhibitor design) (Alfonso-Prieto et al. JACS 2009, 131, )
11 2. Mechanisms of substrate specificity in aldo-keto reductases (AKRs) Reduction of carbonyl compounds (aldehydes and ketones) AKR -C=O -C-OH Substrates: lipids, steroids, cathecolamines, prostaglandins, retinoids,...
12 Human small intestine aldose reductase (AKR1B10) New findings: 1. Detected in large amounts in certain types of lung cancer possible diagnosis marker 2. Activity with retinaldehyde (a precursor of retinoic acid, RA, an anticancer agent) Up-regulation of AKR1B10 activity in cancer could be related with decrease of RA levels Fukumoto et al. Clin. Cancer Res. 11, 1776 (2005) Sheetz & King, J. Am. Med. Assoc. 288, 2579 (2002) Gallego et al. Biochem. J. 2006, 399, 101 Seeking for AKRB10 inhibitors - understanding the basis of substrate recognition
13 Kinetic data aldo-keto reductases The activity of AKR1B10 has been evaluated with substrates of different sizes. OH O 1 Gliceraldehyde (1) OH ze si 9 cis retinaldehyde (2) All trans retinaldehyde (3) O 2 O 3 (O. Gallego, J. Ruiz, J. Farrés, X. Parés, UAB)
14 Kinetic data aldo-keto reductases (O. Gallego, J. Ruiz, J. Farrés, X. Parés, UAB) K cat, min 1 AKR1B10 Aldose reductase (65% homology to AKR1B10 and involved in diabetes) AKR1B1 D,L-Glyceraldehyde 35 ± 1 31 ± 1 9-cis-retinaldehyde 0.9 ± ± 0.1 all-trans-retinaldehyde 27 ± 1 035± What are the structural determinants of AKR1B10 specificity for all trans retinaldehyde?
15 Initial structure for the calculations aldo-keto reductases loop B loop C loop A AKR1B10 structure in complex with iha non specific inhibitor (I. Fita, IRB-CSIC)
16 Calculations aldo-keto reductases Inhibitor (I) Substrate (S) 1) Remove I 2) Docking of S 3) MD AKR1B1/S cis AKR1B10/S cis AKR1B1/S trans AKR1B10/S trans Programs: AUTODOCK, NAMD 100 ns MD, 10 5 h MN (2 months, 128/256 procs).
17 Results AKR1B10 in complex with retinaldehyde Flipping of Lys125 side chain + conformational change of loop A No such change is observed in AKR1B1 (Leu125) Lys125 Lys125 is the key residue (confirmed by site directed mutagenesis) all-trans-retinaldehyde 9-cis-retinaldehyde Gallego et al. PNAS, 104, (2007); Ruiz et al. Chem. Biol. Inter. 178, 171 (2009) loop A
18 Coworkers Mercedes Alfonso-Prieto (PCB, Barcelona) Pietro Vidossich (PCB, Barcelona) Albert Ardèvol (PCB, Barcelona) Experimental collaborators: Ignacio Fita (IRB-CSIC, Barcelona) Peter C. Loewen (U. Manitoba, Canada) Xavier Parés, Jaume Farrés (UAB, Barcelona)
A first principles study of the binding of formic acid in catalase complementing high resolution X-ray structures
Chemical Physics 323 (2006) 129 137 www.elsevier.com/locate/chemphys A first principles study of the binding of formic acid in catalase complementing high resolution X-ray structures Carme Rovira a, *,
More informationQM/MM study on inhibitor of HIV-1 protease. Graduate School of Science, Kyoto University Masahiko Taguchi, Masahiko Kaneso, Shigehiko Hayashi
QM/MM study on inhibitor of HIV-1 protease Graduate School of Science, Kyoto University Masahiko Taguchi, Masahiko Kaneso, Shigehiko Hayashi HIV Human Immunodeficiency Virus Origin of AIDS HIV appearing
More informationStructural Perspectives on Drug Resistance
Structural Perspectives on Drug Resistance Irene Weber Departments of Biology and Chemistry Molecular Basis of Disease Program Georgia State University Atlanta, GA, USA What have we learned from 20 years
More informationChapter 15: Enyzmatic Catalysis
Chapter 15: Enyzmatic Catalysis Voet & Voet: Pages 496-508 Slide 1 Catalytic Mechanisms Catalysis is a process that increases the rate at which a reaction approaches equilibrium Rate enhancement depends
More informationDr. Yonca Yuzugullu PERG (Protein Engineering Research Group)
Dr. Yonca Yuzugullu PERG (Protein Engineering Research Group) BSc, 1997 Ankara University, Turkey PhD, 2010 Middle East Technical University, Turkey Lecturer in Department of Biology Kocaeli University,
More informationSelective oxidation reactions using dioxygen (O2) as the
Oxygen Binding to Catalase-Peroxidase Pietro Vidossich,*,,^ Xavi Carpena, Peter C. Loewen, # Ignacio Fita, and Carme Rovira*, Laboratori de Simulacio Computacional i Modelitzacio, Parc Científic de Barcelona,
More informationSUPPLEMENTARY MATERIAL. Supplementary material and methods:
Electronic Supplementary Material (ESI) for Catalysis Science & Technology. This journal is The Royal Society of Chemistry 2015 SUPPLEMENTARY MATERIAL Supplementary material and methods: - Computational
More informationDimer Dissociation of a Photoreceptor Protein from QM/MM and MD Simulations
Dimer Dissociation of a Photoreceptor Protein from QM/MM and MD Simulations IMA University of Minnesota Minneapolis, MN, July 20, 2015 Haisheng Ren Advisor: Prof. Jiali Gao Department of Chemistry, University
More informationIdentifying Interaction Hot Spots with SuperStar
Identifying Interaction Hot Spots with SuperStar Version 1.0 November 2017 Table of Contents Identifying Interaction Hot Spots with SuperStar... 2 Case Study... 3 Introduction... 3 Generate SuperStar Maps
More informationA. Reaction Mechanisms and Catalysis (1) proximity effect (2) acid-base catalysts (3) electrostatic (4) functional groups (5) structural flexibility
(P&S Ch 5; Fer Ch 2, 9; Palm Ch 10,11; Zub Ch 9) A. Reaction Mechanisms and Catalysis (1) proximity effect (2) acid-base catalysts (3) electrostatic (4) functional groups (5) structural flexibility B.
More informationLecture 15: Enzymes & Kinetics. Mechanisms ROLE OF THE TRANSITION STATE. H-O-H + Cl - H-O δ- H Cl δ- HO - + H-Cl. Margaret A. Daugherty.
Lecture 15: Enzymes & Kinetics Mechanisms Margaret A. Daugherty Fall 2004 ROLE OF THE TRANSITION STATE Consider the reaction: H-O-H + Cl - H-O δ- H Cl δ- HO - + H-Cl Reactants Transition state Products
More informationQM/MM for BIO applications
QM/MM for BIO applications February 9, 2011 I-Feng William Kuo kuo2@llnl.gov, P. O. Box 808, Livermore, CA 94551 This work performed under the auspices of the U.S. Department of Energy by under Contract
More informationVolume 12(2)
Open access www.bioinformation.net Volume 12(2) Hypothesis Insights from molecular modeling, docking and simulation of imidazole nucleus containing chalcones with EGFR kinase domain for improved binding
More informationG. GENERAL ACID-BASE CATALYSIS
G. GENERAL ACID-BASE CATALYSIS Towards a Better Chemical Mechanism via Catalysis There are two types of mechanisms we ll be discussing this semester. Kinetic mechanisms are concerned with rate constants
More informationLecture 14 (10/18/17) Lecture 14 (10/18/17)
Lecture 14 (10/18/17) Reading: Ch6; 190-191, 194-195, 197-198 Problems: Ch6 (text); 7, 24 Ch6 (study guide-facts); 4, 13 NEXT Reading: Ch6; 198-203 Ch6; Box 6-1 Problems: Ch6 (text); 8, 9, 10, 11, 12,
More information2 4 Chemical Reactions and Enzymes Chemical Reactions
Chemical Reactions A chemical reaction occurs when chemical bonds are broken and reformed. Rust forms very slowly, while rocket fuel combustion is explosive! The significance of this comparison is that
More informationRedox cycling. basic concepts of redox biology
Redox cycling basic concepts of redox biology, MD PhD Division of Biochemistry Medical Biochemistry and Biophysics Karolinska Institutet Stockholm, Sweden Elias.Arner@ki.se What is redox? Redox: Reduction
More informationAn introduction to Molecular Dynamics. EMBO, June 2016
An introduction to Molecular Dynamics EMBO, June 2016 What is MD? everything that living things do can be understood in terms of the jiggling and wiggling of atoms. The Feynman Lectures in Physics vol.
More informationMembrane Proteins: 1. Integral proteins: 2. Peripheral proteins: 3. Amphitropic proteins:
Membrane Proteins: 1. Integral proteins: proteins that insert into/span the membrane bilayer; or covalently linked to membrane lipids. (Interact with the hydrophobic part of the membrane) 2. Peripheral
More informationProtein Dynamics. The space-filling structures of myoglobin and hemoglobin show that there are no pathways for O 2 to reach the heme iron.
Protein Dynamics The space-filling structures of myoglobin and hemoglobin show that there are no pathways for O 2 to reach the heme iron. Below is myoglobin hydrated with 350 water molecules. Only a small
More informationChemistry Problem Set #9 Due on Thursday 11/15/18 in class.
Chemistry 391 - Problem Set #9 Due on Thursday 11/15/18 in class. Name 1. There is a real enzyme called cocaine esterase that is produced in bacteria that live at the base of the coca plant. The enzyme
More informationTwo requirements for life: Self-replication and appropriate catalysis. A. Most enzymes (def.: biological catalysts) are proteins
Enzymes We must be able to enhance the rates of many physical and chemical processes to remain alive and healthy. Support for that assertion: Maladies of genetic origin. Examples: Sickle-cell anemia (physical)
More informationExam 3 Review (4/12/2011) Lecture note excerpt covering lectures (Exam 3 topics: Chapters 8, 12, 14 & 15)
Exam 3 Review (4/12/2011) Lecture note excerpt covering lectures 17-23 (Exam 3 topics: Chapters 8, 12, 14 & 15) Enzyme Kinetics, Inhibition, and Regulation Chapter 12 Enzyme Kinetics When the concentration
More information2 4 Chemical Reactions and Enzymes Slide 1 of 34
2 4 Chemical Reactions and Enzymes 1 of 34 Chemical Reactions Chemical Reactions A chemical reaction is a process that changes one set of chemicals into another set of chemicals. Some chemical reactions
More informationCentral Dogma. modifications genome transcriptome proteome
entral Dogma DA ma protein post-translational modifications genome transcriptome proteome 83 ierarchy of Protein Structure 20 Amino Acids There are 20 n possible sequences for a protein of n residues!
More informationPROTEIN EVOLUTION AND PROTEIN FOLDING: NON-FUNCTIONAL CONSERVED RESIDUES AND THEIR PROBABLE ROLE
PROTEIN EVOLUTION AND PROTEIN FOLDING: NON-FUNCTIONAL CONSERVED RESIDUES AND THEIR PROBABLE ROLE O.B. PTITSYN National Cancer Institute, NIH, Laboratory of Experimental & Computational Biology, Molecular
More informationReferences on Kinetics and Mechanisms
References on Kinetics and Mechanisms Excellent reference for all aspects of enzyme kinetics including important elements of Metabolic Control Analysis of relevance to systems analysis of enzyme function
More informationNMR study of complexes between low molecular mass inhibitors and the West Nile virus NS2B-NS3 protease
University of Wollongong Research Online Faculty of Science - Papers (Archive) Faculty of Science, Medicine and Health 2009 NMR study of complexes between low molecular mass inhibitors and the West Nile
More information2013 W. H. Freeman and Company. 6 Enzymes
2013 W. H. Freeman and Company 6 Enzymes CHAPTER 6 Enzymes Key topics about enzyme function: Physiological significance of enzymes Origin of catalytic power of enzymes Chemical mechanisms of catalysis
More informationExperimental and Computational Mutagenesis to Investigate the. Positioning of a General Base within an Enzyme Active Site
Experimental and Computational Mutagenesis to Investigate the Positioning of a General Base within an Enzyme Active Site Jason P. Schwans, Philip Hanoian, Benjamin J. Lengerich, Fanny Sunden, Ana Gonzalez
More informationONETEP PB/SA: Application to G-Quadruplex DNA Stability. Danny Cole
ONETEP PB/SA: Application to G-Quadruplex DNA Stability Danny Cole Introduction Historical overview of structure and free energy calculation of complex molecules using molecular mechanics and continuum
More informationStructure Investigation of Fam20C, a Golgi Casein Kinase
Structure Investigation of Fam20C, a Golgi Casein Kinase Sharon Grubner National Taiwan University, Dr. Jung-Hsin Lin University of California San Diego, Dr. Rommie Amaro Abstract This research project
More informationFast, Faster, Fastest: Exploring Chemical Catalysis
Fast, Faster, Fastest: Exploring Chemical Catalysis Used with the permission of Dr. Russell Larsen, Department of Chemistry, University of Iowa with special thanks to the Fall Semester CHM 33 FS02 Teaching
More informationCitation for the original published paper (version of record):
http://www.diva-portal.org Postprint This is the accepted version of a paper published in Journal of Chemical Theory and Computation. This paper has been peer-reviewed but does not include the final publisher
More informationMulti-scale approaches in description and design of enzymes
Multi-scale approaches in description and design of enzymes Anastassia Alexandrova and Manuel Sparta UCLA & CNSI Catalysis: it is all about the barrier The inside-out protocol: Big Aim: development of
More informationHenderson - Hasselbalch equation
Structure & Properties of Water Bent geometry, O- bond length of 0.958Å Can form ydrogen bonds Comprehensive Exam eview 12/03/2009 enderson - asselbalch equation From [ ][ ] K = [ ] The 6 step approach
More informationEnzyme function: the transition state. Enzymes & Kinetics V: Mechanisms. Catalytic Reactions. Margaret A. Daugherty A B. Lecture 16: Fall 2003
Lecture 16: Enzymes & Kinetics V: Mechanisms Margaret A. Daugherty Fall 2003 Enzyme function: the transition state Catalytic Reactions A B Catalysts (e.g. enzymes) act by lowering the transition state
More informationCatalytic Reactions. Intermediate State in Catalysis. Lecture 16: Catalyzed reaction. Uncatalyzed reaction. Enzymes & Kinetics V: Mechanisms
Enzyme function: the transition state Catalytic Reactions Lecture 16: Enzymes & Kinetics V: Mechanisms Margaret A. Daugherty Fall 2003 A B Catalysts (e.g. enzymes) act by lowering the transition state
More informationRetrieving hits through in silico screening and expert assessment M. N. Drwal a,b and R. Griffith a
Retrieving hits through in silico screening and expert assessment M.. Drwal a,b and R. Griffith a a: School of Medical Sciences/Pharmacology, USW, Sydney, Australia b: Charité Berlin, Germany Abstract:
More information*Corresponding Author *K. F.: *T. H.:
Theoretical Analysis of Activity Cliffs among Benzofuranone Class Pim1 Inhibitors Using the Fragment Molecular Orbital Method with Molecular Mechanics Poisson-Boltzmann Surface Area (FMO+MM-PBSA) Approach
More informationSupporting Information
S1 Supporting Information Unraveling the Reaction Mechanism of Enzymatic C5-Cytosine Methylation of DNA. A Combined Molecular Dynamics and QM/MM Study of Wild Type and Gln119 Variant Juan Aranda 1, Kirill
More informationRanjit P. Bahadur Assistant Professor Department of Biotechnology Indian Institute of Technology Kharagpur, India. 1 st November, 2013
Hydration of protein-rna recognition sites Ranjit P. Bahadur Assistant Professor Department of Biotechnology Indian Institute of Technology Kharagpur, India 1 st November, 2013 Central Dogma of life DNA
More informationCatalytic power of enzymes
Enzyme catalysis Catalytic power of enzymes Enzymatic reactions are involved in most biological processes. There is a major practical and fundamental interest in finding out what makes enzymes so efficient
More informationChapter 4: Amino Acids
Chapter 4: Amino Acids All peptides and polypeptides are polymers of alpha-amino acids. lipid polysaccharide enzyme 1940s 1980s. Lipids membrane 1960s. Polysaccharide Are energy metabolites and many of
More informationChapter 17. Reactions of Organic Functional Groups Part 2. Reactions of Organic Functional Groups Part 2- page 1
Chapter 17 Reactions of rganic Functional Groups art 2 Reactions of rganic Functional Groups art 2- page 1 Rxns of rganic Functional Groups art 2: Redox A Closer Look xidation & Reduction Reactions of
More informationReview of General & Organic Chemistry
Review of General & Organic Chemistry Diameter of a nucleus is only about 10-15 m. Diameter of an atom is only about 10-10 m. Fig 3.1 The structure of an atom Periodic Table, shown below, is a representation
More informationSupplementary figure 1. Comparison of unbound ogm-csf and ogm-csf as captured in the GIF:GM-CSF complex. Alignment of two copies of unbound ovine
Supplementary figure 1. Comparison of unbound and as captured in the GIF:GM-CSF complex. Alignment of two copies of unbound ovine GM-CSF (slate) with bound GM-CSF in the GIF:GM-CSF complex (GIF: green,
More informationLecture 11: Enzymes: Kinetics [PDF] Reading: Berg, Tymoczko & Stryer, Chapter 8, pp
Lecture 11: Enzymes: Kinetics [PDF] Reading: Berg, Tymoczko & Stryer, Chapter 8, pp. 216-225 Updated on: 2/4/07 at 9:00 pm Key Concepts Kinetics is the study of reaction rates. Study of enzyme kinetics
More informationSUPPLEMENTARY FIGURES. Figure S1
SUPPLEMENTARY FIGURES Figure S1 The substrate for DH domain (2R,3R,4R,6R,7S,8S,9R)-3,7,9-trihydroxy-5-oxo-2,4,6,8 tetramethylundecanoate) was docked as two separate fragments shown in magenta and blue
More informationChem Lecture 3 Hemoglobin & Myoglobin
Chem 452 - Lecture 3 Hemoglobin & Myoglobin 111003 Hemoglobin (Hb) and Myoglobin (Mb) function as oxygen transport and storage molecules in higher organisms. There functions have been long studied and,
More informationBiotechnology of Proteins. The Source of Stability in Proteins (III) Fall 2015
Biotechnology of Proteins The Source of Stability in Proteins (III) Fall 2015 Conformational Entropy of Unfolding It is The factor that makes the greatest contribution to stabilization of the unfolded
More informationEXPERIMENT THREE - Fast, Faster, Fastest: Exploring Chemical Catalysis
EXPERIMENT TREE - Fast, Faster, Fastest: Exploring Chemical Catalysis Used with the permission of Dr. Russell Larsen, Department of Chemistry, University of Iowa with special thanks to the Fall Semester
More informationRetinal Proteins (Rhodopsins) Vision, Bioenergetics, Phototaxis. Bacteriorhodopsin s Photocycle. Bacteriorhodopsin s Photocycle
Molecular chanisms of Photoactivation and Spectral Tuning in Retinal Proteins Emad Tajkhorshid Theoretical and Computational Biophysics Group Beckman Institute University of Illinois at Urbana-Champaign
More informationNH 2. Biochemistry I, Fall Term Sept 9, Lecture 5: Amino Acids & Peptides Assigned reading in Campbell: Chapter
Biochemistry I, Fall Term Sept 9, 2005 Lecture 5: Amino Acids & Peptides Assigned reading in Campbell: Chapter 3.1-3.4. Key Terms: ptical Activity, Chirality Peptide bond Condensation reaction ydrolysis
More informationSUPPLEMENTARY INFORMATION
doi:10.1038/nature17991 Supplementary Discussion Structural comparison with E. coli EmrE The DMT superfamily includes a wide variety of transporters with 4-10 TM segments 1. Since the subfamilies of the
More informationFinal Chem 4511/6501 Spring 2011 May 5, 2011 b Name
Key 1) [10 points] In RNA, G commonly forms a wobble pair with U. a) Draw a G-U wobble base pair, include riboses and 5 phosphates. b) Label the major groove and the minor groove. c) Label the atoms of
More informationC a h p a t p e t r e r 6 E z n y z m y e m s
Chapter 6 Enzymes 4. Examples of enzymatic reactions acid-base catalysis: give and take protons covalent catalysis: a transient covalent bond is formed between the enzyme and the substrate metal ion catalysis:
More informationJournal of Pharmacology and Experimental Therapy-JPET#172536
A NEW NON-PEPTIDIC INHIBITOR OF THE 14-3-3 DOCKING SITE INDUCES APOPTOTIC CELL DEATH IN CHRONIC MYELOID LEUKEMIA SENSITIVE OR RESISTANT TO IMATINIB Manuela Mancini, Valentina Corradi, Sara Petta, Enza
More informationElectronic Supplementary Information Effective lead optimization targeted for displacing bridging water molecule
Electronic Supplementary Material (ESI) for Physical Chemistry Chemical Physics. This journal is the Owner Societies 2018 Electronic Supplementary Information Effective lead optimization targeted for displacing
More informationEnvironment Research Institute, Shandong University, Jinan , P. R. China. Keywords
Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 2015 Supplementary data for Dehydrochlorination mechanism of γ- hexachlorocyclohexane degraded by
More informationChapter 6: Outline-2. Chapter 6: Outline Properties of Enzymes. Introduction. Activation Energy, E act. Activation Energy-2
Chapter 6: Outline- Properties of Enzymes Classification of Enzymes Enzyme inetics Michaelis-Menten inetics Lineweaver-Burke Plots Enzyme Inhibition Catalysis Catalytic Mechanisms Cofactors Chapter 6:
More informationAside on Chapter 22, Organic Chemistry. Why is organic chemistry important:
Aside on Chapter 22, Organic Chemistry Why is organic chemistry important: 1) Materials 2) Energy (oil & coal) 3) Human health a) diagnosis b) treatment (drugs) 4) A drug development logic progression
More informationEnzymes I. Dr. Mamoun Ahram Summer semester,
Enzymes I Dr. Mamoun Ahram Summer semester, 2017-2018 Resources Mark's Basic Medical Biochemistry Other resources NCBI Bookshelf: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books The Medical Biochemistry
More informationAn Introduction to Metabolism. Chapter 8
An Introduction to Metabolism Chapter 8 METABOLISM I. Introduction All of an organism s chemical reactions Thousands of reactions in a cell Example: digest starch use sugar for energy and to build new
More informationTyr-51 is the proton donor acceptor for NAD(H)-dependent interconversion of xylose and xylitol by Candida tenuis xylose reductase (AKR2B5)
Tyr-51 is the proton donor acceptor for NAD(H)-dependent interconversion of xylose and xylitol by Candida tenuis xylose reductase (AKR2B5) Simone L. Pival, Mario Klimacek, Regina Kratzer, Bernd Nidetzky
More informationBIOCHEMISTRY. František Vácha. JKU, Linz.
BIOCHEMISTRY František Vácha http://www.prf.jcu.cz/~vacha/ JKU, Linz Recommended reading: D.L. Nelson, M.M. Cox Lehninger Principles of Biochemistry D.J. Voet, J.G. Voet, C.W. Pratt Principles of Biochemistry
More informationA catalase-peroxidase from a newly isolated thermoalkaliphilic Bacillus sp. with potential for the treatment of textile bleaching effluents
A catalase-peroxidase from a newly isolated thermoalkaliphilic Bacillus sp. with potential for the treatment of textile bleaching effluents Marinka Gudelj, Gilbert Otto Fruhwirth, Andreas Paar, Fritz Lottspeich,
More informationMITOCHONDRIAL LAB. We are alive because we make a lot of ATP and ATP makes (nonspontaneous) chemical reactions take place
MITOCHONDRIAL LAB We are alive because we make a lot of ATP and ATP makes (nonspontaneous) chemical reactions take place We make about 95% of our ATP in the mitochondria We will isolate mitochondria, and
More informationUnraveling the degradation of artificial amide bonds in Nylon oligomer hydrolase: From induced-fit to acylation processes
Electronic Supplementary Material (ESI) for Physical Chemistry Chemical Physics. This journal is the Owner Societies 2015 Supporting Information for Unraveling the degradation of artificial amide bonds
More informationCatalysis. Instructor: Dr. Tsung-Lin Li Genomics Research Center Academia Sinica
Catalysis Instructor: Dr. Tsung-Lin Li Genomics Research Center Academia Sinica References: Biochemistry" by Donald Voet and Judith G. Voet Biochemistry" by Christopher K. Mathews, K. E. Van Hold and Kevin
More informationSupporting information to: Time-resolved observation of protein allosteric communication. Sebastian Buchenberg, Florian Sittel and Gerhard Stock 1
Supporting information to: Time-resolved observation of protein allosteric communication Sebastian Buchenberg, Florian Sittel and Gerhard Stock Biomolecular Dynamics, Institute of Physics, Albert Ludwigs
More informationBiophysics 490M Project
Biophysics 490M Project Dan Han Department of Biochemistry Structure Exploration of aa 3 -type Cytochrome c Oxidase from Rhodobacter sphaeroides I. Introduction: All organisms need energy to live. They
More informationOrganic Chemistry of Drug Degradation
Organic Chemistry of Drug Degradation Li New Jersey Email: minli88@yahoo.com Publishing Contents Chapter 1 Introduction 1 1.1 Drug Impurities, and the Importance of Understanding Drug Chemistry 1 Characteristics
More informationREACTION AND SYNTHESIS REVIEW
REACTION AND SYNTHESIS REVIEW A STUDENT SHOULD BE ABLE TO PREDICT PRODUCTS, IDENTIFY REACTANTS, GIVE REACTION CONDITIONS, PROPOSE SYNTHESES, AND PROPOSE MECHANISMS (AS LISTED BELOW). REVIEW THE MECHANISM
More informationCHEMISTRY 332 FALL 08 EXAM I September 24-25, 2008
First Three Letters of Last ame AME etwork ID EMISTRY 332 FALL 08 EXAM I September 24-25, 2008 The following materials are permissible during the exam: molecular model kits, course notes (printed, electronic,
More information1. What is an ångstrom unit, and why is it used to describe molecular structures?
1. What is an ångstrom unit, and why is it used to describe molecular structures? The ångstrom unit is a unit of distance suitable for measuring atomic scale objects. 1 ångstrom (Å) = 1 10-10 m. The diameter
More informationCHEM 109A Organic Chemistry
CHEM 109A Organic Chemistry https://labs.chem.ucsb.edu/zakarian/armen/courses.html Chapter 5 Alkene: Introduction Thermodynamics and Kinetics Midterm 2... Grades will be posted on Tuesday, Feb. 27 th.
More informationBiology Slide 1 of 34
Biology 1 of 34 2 4 Chemical Reactions and Enzymes 2 of 34 2 4 Chemical Reactions and Enzymes Chemical Reactions Chemical Reactions A chemical reaction is a process that changes one set of chemicals into
More informationCHEM 251 (4 credits): Description
CHEM 251 (4 credits): Intermediate Reactions of Nucleophiles and Electrophiles (Reactivity 2) Description: An understanding of chemical reactivity, initiated in Reactivity 1, is further developed based
More informationA Thesis Presented to The Academic Faculty. Miranda McDaniel
Proton Coupled Electron Transfer as Explored by the Tryptophan Cation Radical Formation in Biomimetic Peptides A Thesis Presented to The Academic Faculty by Miranda McDaniel In Partial Fulfillment of the
More informationBiochemistry 462a - Enzyme Kinetics Reading - Chapter 8 Practice problems - Chapter 8: (not yet assigned); Enzymes extra problems
Biochemistry 462a - Enzyme Kinetics Reading - Chapter 8 Practice problems - Chapter 8: (not yet assigned); Enzymes extra problems Introduction Enzymes are Biological Catalysis A catalyst is a substance
More information!n[a] =!n[a] o. " kt. Half lives. Half Life of a First Order Reaction! Pressure of methyl isonitrile as a function of time!
Half lives Half life: t 1/2 t 1/2 is the time it takes for the concentration of a reactant to drop to half of its initial value. For the reaction A! products Half Life of a First Order Reaction! Pressure
More informationEnzymes Enzyme Mechanism
Mechanisms of Enzymes BCMB 3100 Chapters 6, 7, 8 Enzymes Enzyme Mechanism 1 Energy diagrams Binding modes of enzyme catalysis Chemical modes of enzyme catalysis Acid-Base catalysis Covalent catalysis Binding
More informationSupramolecular catalysis
Supramolecular catalysis Catalyst: a chemical species that accelerates a chemical reactions without being consumed rganometallic catalyst: soluble metal complex with organic ligands that accelerates the
More informationINTERACTIONS BETWEEN GLYCOSYLTRANSFERASES AND 2-DEOXY GLYCOSYL DERIVATIVES OF URIDINE SIMULATED BY MOLECULAR DOCKING
Acta Poloniae Pharmaceutica ñ Drug Research, Vol. 65 No. 6 pp. 735ñ741, 2008 ISSN 0001-6837 Polish Pharmaceutical Society INTERACTIONS BETWEEN GLYCOSYLTRANSFERASES AND 2-DEOXY GLYCOSYL DERIVATIVES OF URIDINE
More informationEnzymes Enzyme Mechanism
BCMB 3100 Chapters 6, 7, 8 Enzymes Enzyme Mechanism 1 Mechanisms of Enzymes Energy diagrams Binding modes of enzyme catalysis Chemical modes of enzyme catalysis Acid-Base catalysis Covalent catalysis Binding
More informationTowards Physics-based Models for ADME/Tox. Tyler Day
Towards Physics-based Models for ADME/Tox Tyler Day Overview Motivation Application: P450 Site of Metabolism Application: Membrane Permeability Future Directions and Applications Motivation Advantages
More informationFrom Friday s material
5.111 Lecture 35 35.1 Kinetics Topic: Catalysis Chapter 13 (Section 13.14-13.15) From Friday s material Le Chatelier's Principle - when a stress is applied to a system in equilibrium, the equilibrium tends
More informationCHEM 112 Name: (Last) (First). Section No.: VISUALIZING ORGANIC REACTIONS THROUGH USE OF MOLECULAR MODELS
CHEM 112 Name: (Last) (First). Section No.: VISUALIZING ORGANIC REACTIONS THROUGH USE OF MOLECULAR MODELS 1) HYDROCARBONS: a. Saturated Hydrocarbons: Construct a model for propane, C 3 H 8, using black
More informationComparison between Bacteriorhodopsin and Halorhodopsin. Halorhodopsin (HR) and Bacteriorhodopsin (BR) belong to a subfamily of
Comparison between Bacteriorhodopsin and Halorhodopsin Halorhodopsin (HR) and Bacteriorhodopsin (BR) belong to a subfamily of heptahelical membrane proteins, the archaeal rhodopsins. They are found in
More informationRadiation Processing. Chemical Effects
Radiation Processing Chemical Effects Reactions ofhydrated Electron Major Reactions of e-aq H 2 0 1. e- aq + N 2 0 N 2 + {)H Used to detect/estimate e- aq and to increase OH yield 2. e- aq + O 2 2-...
More informationL718Q mutant EGFR escapes covalent inhibition by stabilizing. a non-reactive conformation of the lung cancer drug. osimertinib
Electronic Supplementary Material (ESI) for Chemical Science. This journal is The Royal Society of Chemistry 2018 Electronic Supplementary Information (ESI) for L718Q mutant EGFR escapes covalent inhibition
More informationModeling the Enantioselective Enzymatic Reaction with Modified Genetic Docking Algorithm
Nonlinear Analysis: Modelling and Control, 2004, Vol. 9, No. 4, 373 383 Modeling the Enantioselective Enzymatic Reaction with Modified Genetic Docking Algorithm A. Žiemys 1,2, L. Rimkutė 1, J. Kulys 2,3
More informationChemical Reactions and Enzymes. (Pages 49-59)
Chemical Reactions and Enzymes (Pages 49-59) Chemical Reactions Chemistry of Life Not just what life is made of. What life does! Chemical Reactions Chemistry of Life Not just what life is made of. What
More informationCatalase-peroxidase KatG of Burkholderia pseudomallei at 1.7 Å resolution
doi:10.1016/s0022-2836(03)00122-0 J. Mol. Biol. (2003) 327, 475 489 Catalase-peroxidase KatG of Burkholderia pseudomallei at 1.7 Å resolution Xavi Carpena 1, Suvit Loprasert 2, Skorn Mongkolsuk 2, Jacek
More informationComputational Modeling of Protein Kinase A and Comparison with Nuclear Magnetic Resonance Data
Computational Modeling of Protein Kinase A and Comparison with Nuclear Magnetic Resonance Data ABSTRACT Keyword Lei Shi 1 Advisor: Gianluigi Veglia 1,2 Department of Chemistry 1, & Biochemistry, Molecular
More informationAchievement of Protein Thermostability by Amino Acid Substitution. 2018/6/30 M1 Majima Sohei
Achievement of Protein Thermostability by Amino Acid Substitution 2018/6/30 M1 Majima Sohei Contents of Today s seminar Introduction Study on hyperthermophilic enzymes to understand the origin of thermostability
More informationEnergy, Enzymes, and Metabolism. Energy, Enzymes, and Metabolism. A. Energy and Energy Conversions. A. Energy and Energy Conversions
Energy, Enzymes, and Metabolism Lecture Series 6 Energy, Enzymes, and Metabolism B. ATP: Transferring Energy in Cells D. Molecular Structure Determines Enzyme Fxn Energy is the capacity to do work (cause
More informationLecture 27. Transition States and Enzyme Catalysis
Lecture 27 Transition States and Enzyme Catalysis Reading for Today: Chapter 15 sections B and C Chapter 16 next two lectures 4/8/16 1 Pop Question 9 Binding data for your thesis protein (YTP), binding
More informationGround Rules of Metabolism CHAPTER 6
Ground Rules of Metabolism CHAPTER 6 Antioxidants You ve heard the term. What s the big deal? Found naturally in many fruits and vegetables Added to many products What do they actually do? Antioxidants
More information