Role of catalytic-residues in enzymatic mechanisms of homologous ketosteroid isomerases

Kyung Seok Oh, Kwan Yong Choi, B. H. Oh, K. S. Kim, S. S. Cha, D. H. Kim, H. S. Cho, N. C. Ha, G. Choi, Jin Yong Lee, P. Tarakeshwar, H. S. Son

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Ketosteroid isomerase (KSI) is one of the most proficient enzymes catalyzing an allylic isomerization reaction at a diffusion-controlled rate. In this study of KSI, we have detailed the structures of its active site, the role of various catalytic residues, and have explained the origin of the its fast reactivity by carrying out a detailed investigation of the enzymatic reaction mechanism. This investigation included the X-ray determination of 15 crystal structures of two homologous enzymes in free and complexed states (with inhibitors) and extensive ab initio calculations of the interactions between the active sites and the reaction intermediates. The catalytic residues, through short strong hydrogen bonds, play the role of charge buffer to stabilize the negative charge built up on the intermediates in the course of the reaction. The hydrogen bond distances in the intermediate analogues are found to be about 0.2 A shorter in the product analogues both experimentally and theoretically.

Original languageEnglish
Pages (from-to)13891-13896
Number of pages6
Issue number45
StatePublished - 14 Nov 2000


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