Studies on the Active Site of Chymotrypsin.

Mechanism-Based Studies of the Active Site-Directed Inhibition and Activation of Enzyme Transketolase

Derivatives of phenyl-keto butenoic acids have been reported to be inhibitors of pyruvate decarboxylase, (PDC). The inhibition of transketolase, a thiamine requiring enzyme such as PDF, by meta nitrophenyl derivative of 2-oxo-3-butenoic acid (MNPB) is reported here. These studies indicate that the inhibitor binds to the enzyme at the active site. A two-step inhibition was observed, first th...

Conformational dynamics at the active site of alpha-chymotrypsin and enzymatic activity.

The role of dynamical flexibility at the active site of a proteolytic enzyme alpha-chymotrypsin (CHT) has been correlated with its catalytic activity. The temperature-dependent efficiency of catalysis reveals a bell-shaped feature with a peak at 37 degrees C, the typical body temperature of homeothermal animals. The overall structural integrity of the enzyme in our experimental temperature rang...

Spin-labeled Sulfonyl Fluorides as Active Site Probes of Protease Structure

a-Chymotrypsin and trypsin were spin-labeled with 14 ortho-, meta-, and para-substituted phenylsulfonyl fluorides. These analogues of tosylfluoride were substituted with either pyrrolidinyl, pyrrolinyl, or piperidinyl nitroxide moieties. A complete description of their synthesis and the enzyme inhibition studies is presented in the following paper (WONG, S. S., QUIGGLE, K., TRIPLETT, C., AND BE...

DFT Studies and Topological Analyses of Electron Density on Acetophenone and Propiophenone Thiosemicarbazone Derivatives as Covalent Inhibitors of Falcipain-2, a Major Plasmodium Falciparum Cysteine Protease

Thiosemicarbazones (TSCs) possess significant antimalarial properties believed to be linked to the inhibition of major cysteine proteases, such as falcipain-2, in Plasmodium falciparum. However, the binding modes of TSCs to the active site of these enzymes are not clear. As a result of this, the nature of the bonding interactions between the active site of falcipain-2 and different derivatives ...

Comparative studies of the specificities of -chymotrypsin and subtilisin BPN'. Studies with flexible and 'locked' substrates.

Subtilisin BPN' hydrolysed N-acetyl-l-3-(2-naphthyl)-alanine methyl ester, N-acetyl-l-leucine methyl ester and N-acetyl-l-valine methyl ester, faster than alpha-chymotrypsin. Of eight ;locked' substrates tested, only methyl 5,6-benzindan-2-carboxylate was hydrolysed faster by subtilisin, whereas the other esters were better substrates for chymotrypsin. Compared with the values for chymotrypsin,...

High resolution nuclear magnetic resonance studies of the active site of chymotrypsin. I. The hydrogen bonded protons of the "charge relay" system.