Document Detail


The polymer basis of kinetics and equilibria of enzymes: the accessible-volume origin of entropy changes in a class Abeta-lactamase.
MedLine Citation:
PMID:  9988524     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The occurrence of enzymatic catalysis, as for any chemical reaction, depends critically upon close contact of the reactants, since making/breaking of bonds occurs over distances of about 0.2 A. Unlike small molecules, each enzyme molecule acts as an ordered solvent and reactant. Each group important to the enzyme reaction interacts with the substrate, then moves away, and subsequently binds another substrate. In other words, the group undergoes round trips in structure. For a round trip, the thermochemical state functions deltaG, deltaH, deltaS, etc., are zero. As a consequence, control of the binding of substrate must reside in the nonbinding conformations of the polymer since they govern the different fractions of time the macromolecule is in the correct conformation for bonding. Applying standard macromolecular models to the enzymes suggests that the majority of free energy for an enzyme reaction resides in the enzyme structure as an entropic contribution. Enthalpic contributions come from bond formation with the substrates and substrate structural changes. Further, it is shown that the molecular mechanisms that can effect binding and allosteric control fall into only three classes. Three x-ray structures of class A beta-lactamases (native, mutant, and with substrate) show the individual binding groups at the active site change their accessible volumes depending on substrate binding and mutant form. From these volume differences, the deltaS of reaction is calculated. The x-ray-derived deltaG = - TdeltaS matches the deltaG = -RT ln k1 from changes in rate constants for the same set of beta-penicillinases.
Authors:
K A Rubinson
Related Documents :
23886934 - Inhibition of cyp1 by berberine, palmatine, and jatrorrhizine: selectivity, kinetic cha...
24912194 - Unitary step of gliding machinery in mycoplasma mobile.
25126694 - Ebselen inhibits hepatitis c virus ns3 helicase binding to nucleic acid and prevents vi...
23012354 - A conformational change of the γ subunit indirectly regulates the activity of cyanobact...
2463104 - Maturation of hagfish gland thread cells: composition and characterization of intermedi...
22923734 - Stable complex formation between serine protease inhibitor and zymogen: coagulation fac...
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of protein chemistry     Volume:  17     ISSN:  0277-8033     ISO Abbreviation:  J. Protein Chem.     Publication Date:  1998 Nov 
Date Detail:
Created Date:  1999-04-29     Completed Date:  1999-04-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8217321     Medline TA:  J Protein Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  771-87     Citation Subset:  IM    
Affiliation:
The Five Oaks Research Institute, Cincinnati, Ohio 45238-5157, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Entropy
Enzymes / chemistry*,  classification,  metabolism*
Kinetics
Models, Chemical*
Normal Distribution
Polymers / chemistry,  metabolism
Protein Binding
Scattering, Radiation
X-Rays
beta-Lactamases / chemistry*,  classification,  metabolism
Chemical
Reg. No./Substance:
0/Enzymes; 0/Polymers; EC 3.5.2.6/beta-Lactamases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Interactions between NFkappaB and its inhibitor ikappaB: biophysical characterization of a NFkappaB/...
Next Document:  Partially folded conformations of inositol monophosphatase endowed with catalytic activity.