Enzymes binding specificity

Natronobacterium magadii (haloalkaliphilic archaeon, enzyme binds specifically to natronobacterial flagellins [38]) [38]... 

Kua J, Zhang Y, McCammon JA (2002) Studying enzyme binding specificity in acetylcholinesterase using a combined molecular dynamics and multiple docking approach. J Am Chem Soc 124(28) 8260-8267... 

Model building also predicts that the Ala 216 mutant would displace a water molecule at the bottom of the specificity pocket that in the wild type enzyme binds to the NH3 group of the substrate Lys side chain (Figure 11.12). The extra CH3 group of this mutant is not expected to disturb the binding of the Arg side chain. One would therefore expect that the Km for Lys... 

T"he extraordinary ability of an enzyme to catalyze only one particular reaction is a quality known as specificity (Chapter 14). Specificity means an enzyme acts only on a specific substance, its substrate, invariably transforming it into a specific product. That is, an enzyme binds only certain compounds, and then, only a specific reaction ensues. Some enzymes show absolute specificity, catalyzing the transformation of only one specific substrate to yield a unique product. Other enzymes carry out a particular reaction but act on a class of compounds. For example, hexokinase (ATP hexose-6-phosphotransferase) will carry out the ATP-dependent phosphorylation of a number of hexoses at the 6-posi-tion, including glucose. 

It has often been questioned whether the rates and kinetics of purified enzymes, determined in very dilute solutions with high concentrations of their substrates, but not always of their cofactors, can be extrapolated to the conditions prevailing in the matrix. Much of the mitochondrial water will be bound to protein by hydrogen bonds and electrostatically, but there is also a pool of free water which may only be a fraction of the total water (Gitomer, 1987). The molar concentrations of intermediates of the citrate cycle and of p-oxidation are very low, usually less than those of most enzymes (Srere, 1987 Watmough et al., 1989 Sumegi et al., 1991). The extent to which cofactors and intermediates bind specifically or nonspecifically to enzymes is not known. It is therefore difficult to estimate concentration of these... 

We have already mentioned the application of supercomputers to biochemical simulations. Internal dynamics may play an Important role In such simulations. An example would be enzyme binding-site fluctuations that modulate reactivity or the dynamics of antigen-antibody association (11). In the specific case of diffusion-controlled processes, molecular recognition may occur because of long-range sterlc effects which are hard to assess without very expensive simulations (12.)-... 

Heparin is an important anticoagulant. It binds with factors IX and XI, but its most important interaction is with plasma antithrombin III (discussed in Chapter 51). Heparin can also bind specifically to lipoprotein lipase present in capillary walls, causing a release of this enzyme into the circulation. 

Most in vitro studies of xanthines have centered around the enzyme xanthine oxidase. Bergmann and co-workers 40-4)) have examined the main oxidative pathways in the xanthine oxidase catalyzed oxidation of purines. The mechanism proposed by these workers 41 > is that the enzyme binds a specific tautomeric form of the substrate, regardless of whether or not that form represents the major structure present in solution. It is then proposed that the purine, e.g., xanthine, undergoes hydration at the N7=C8 double bond either prior to or simultaneously with dehydrogenation of the same position. Accordingly, the process would involve either pathway a or b. Fig. 15. Route a would give a lactim form of the oxidized purine, while b would give the cor-... 

Hydrazide groups can react with carbonyl groups to form stable hydrazone linkages. Derivatives of proteins formed from the reaction of their carboxylate side chains with adipic acid dihydrazide (Chapter 4, Section 8.1) and the water-soluble carbodiimide EDC (Chapter 3, Section 1.1) create activated proteins that can covalently bind to formyl residues. Hydrazide-modified enzymes prepared in this manner can bind specifically to aldehyde groups formed by mild periodate oxidation of carbohydrates (Chapter 1, Section 4.4). These reagents can be used in assay systems to detect or measure glycoproteins in cells, tissue sections, or blots (Gershoni et al., 1985). 

In this model, the binding of the substrate to the enzyme strains specific chemical bonds, making the subsequent chemical reaction easier. If a bond has to be broken, the enzyme grabs onto both sides of the bond and pulls. If a bond has to be formed, the enzyme grabs onto both sides and pushes. By this model, the enzyme must be designed to apply the strain in the right direction—the direction that will help convert the reactant to the transition state (Fig. 7-5). 

Allosteric inhibitors bind specifically to the T state and make it harder for substrate to switch enzyme into the R state. 

Allosteric activators bind specifically to the R state and pull more of the enzyme into the more active R state. 

An enzyme is an organic molecule, specifically a protein, that catalyzes a chemical reaction. Or, more simply, an enzyme is a biological catalyst. The enzyme binds with a reactant species, known as the substrate, to form a reactive intermediate species. While bound, the substrate can transform to a reaction product that would not form, or form very slowly, in the absence of the enzyme. 

Enzyme-stabilized single-stranded DNA (known as the open complex) is the first intermediate formed in transcription initiation of RNA polymerases its formation is the rate-limiting step. Designing molecules which bind specifically to the open complex is a strategy for generating potent transcription inhibitors. The redox-stable complex of Cu(I) with 1,2-dimethyl- 1,10-phenanthroline is an example of such a strategy (405). The Cu(I) complex binds specifically to the single-stranded DNA of transcriptional open complexes and is an effective inhibitor of eukaryotic and prokaryotic transcription. 

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