THE CHEMICAL MODIFICATION OF CHYMOTRYPSIN

1964 ◽  
Vol 42 (6) ◽  
pp. 695-714 ◽  
Author(s):  
G. H. Dixon ◽  
H. Schachter
Keyword(s):  
Enzyme Activity ◽  
Amino Acid ◽  
Chemical Modification ◽  
Active Site ◽  
Specific Binding ◽  
Bond Breaking ◽  
Kinetic Properties ◽  
Side Chains ◽  
Amino Acid Side Chains

Chemical modification of chymotrypsin has led to the identification of several amino acid side-chains which are probably constituents of the active site of the enzyme. A single seryl and a single histidyl residue appear to cooperate in catalyzing the bond-breaking process while one or more tryptophanyl residues may be involved in the specific binding of substrate. Neither of the two methionyl residues is essential for enzyme activity although changes in kinetic properties occur when they are modified by oxidation or alkylation.

The Effect of Modification on the Susceptibility of Collagen to Proteolysis: I. Chemical Modification of Amino Acid Side Chains

Matrix ◽  
1991 ◽  
Vol 11 (5) ◽  
pp. 321-329 ◽  
Author(s):  
A.M. Diamond ◽  
S.D. Gorham ◽  
D.J. Etherington ◽  
J.G. Robertson ◽  
N.D. Light
Keyword(s):  
Amino Acid ◽  
Chemical Modification ◽  
Side Chains ◽  
Amino Acid Side Chains

Controlling the reactivity of radical intermediates by coenzyme B12-dependent methylmalonyl-CoA mutase

2002 ◽  
Vol 30 (4) ◽  
pp. 621-624 ◽  
Author(s):  
R. Banerjee ◽  
M. Vlasie
Keyword(s):  
Amino Acid ◽  
Small Group ◽  
Active Site ◽  
Side Chains ◽  
Coenzyme B12 ◽  
Structural Studies ◽  
Radical Chemistry ◽  
Radical Intermediates ◽  
Amino Acid Side Chains ◽  
Rearrangement Reactions

Adenosylcobalamin or coenzyme B12-dependent enzymes are members of the still relatively small group of radical enzymes and catalyse 1,2-rearrangement reactions. A member of this family is methylmalonyl-CoA mutase, which catalyses the isomerization of methylmalonyl-CoA to succinyl-CoA and, unlike the others, is present in both bacteria and animals. Enzymes that catalyse some of the most chemically challenging reactions are the ones that tend to deploy radical chemistry. The use of radical intermediates in an active site lined with amino acid side chains that threaten to extinguish the reaction by presenting alternative groups for abstraction poses the conundrum of how the enzymes control their reactivity. In this review, insights into this issue that have emerged from kinetic, mutagenesis and structural studies are described for methylmalonyl-CoA mutase.

scholarly journals Enzyme Architecture: Amino Acid Side-Chains That Function To Optimize the Basicity of the Active Site Glutamate of Triosephosphate Isomerase

2018 ◽  
Vol 140 (26) ◽  
pp. 8277-8286 ◽  
Author(s):  
Xiang Zhai ◽  
Christopher J. Reinhardt ◽  
M. Merced Malabanan ◽  
Tina L. Amyes ◽  
John P. Richard
Keyword(s):  
Amino Acid ◽  
Active Site ◽  
Triosephosphate Isomerase ◽  
Side Chains ◽  
Amino Acid Side Chains

scholarly journals Ionic properties of an essential histidine residue in pig heart lactate dehydrogenase

1973 ◽  
Vol 131 (4) ◽  
pp. 729-738 ◽  
Author(s):  
J. John Holbrook ◽  
V. Ann Ingram
Keyword(s):  
Enzyme Activity ◽  
Amino Acid ◽  
Lactate Dehydrogenase ◽  
Side Chains ◽  
Histidine Residue ◽  
Acylating Agent ◽  
Diethyl Pyrocarbonate ◽  
Substrate Analogues ◽  
Amino Acid Side Chains

1. Pig heart lactate dehydrogenase is inhibited by addition of one equivalent of diethyl pyrocarbonate. The inhibition is due to the acylation of a unique histidine residue which is 10-fold more reactive than free histidine. No other amino acid side chains are modified. 2. The carbethoxyhistidine residue slowly decomposes and the enzyme activity reappears. 3. The essential histidine residue is only slightly protected by the presence of NADH but is completely protected when substrate and substrate analogues bind to the enzyme–NADH complex. The protection is interpreted in terms of a model in which substrates can only bind to the enzyme in which the histidine residue is protonated and is thus not available for reaction with the acylating agent. 4. The apparent pKa of the histidine residue in the apoenzyme is 6.8±0.2. In the enzyme–NADH complex it is 6.7±0.2. 5. Acylated enzyme binds NADH with unchanged affinity. The enzyme is inhibited because substrates and substrate analogues cannot bind at the acylated histidine residue in the enzyme–NADH complex.

Predicting the Strength of Stacking Interactions Between Heterocycles and Aromatic Amino Acid Side Chains

2019 ◽  
Author(s):  
Andrea N. Bootsma ◽  
Analise C. Doney ◽  
Steven Wheeler
Keyword(s):  
Amino Acid ◽  
Binding Sites ◽  
Aromatic Amino Acid ◽  
Aromatic Amino Acids ◽  
Biologically Active ◽  
Side Chains ◽  
Stacking Interactions ◽  
Inhibitor Binding ◽  
Protein Binding Sites ◽  
Amino Acid Side Chains

<p>Despite the ubiquity of stacking interactions between heterocycles and aromatic amino acids in biological systems, our ability to predict their strength, even qualitatively, is limited. Based on rigorous <i>ab initio</i> data, we have devised a simple predictive model of the strength of stacking interactions between heterocycles commonly found in biologically active molecules and the amino acid side chains Phe, Tyr, and Trp. This model provides rapid predictions of the stacking ability of a given heterocycle based on readily-computed heterocycle descriptors. We show that the values of these descriptors, and therefore the strength of stacking interactions with aromatic amino acid side chains, follow simple predictable trends and can be modulated by changing the number and distribution of heteroatoms within the heterocycle. This provides a simple conceptual model for understanding stacking interactions in protein binding sites and optimizing inhibitor binding in drug design.</p>

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