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Modeling substrate binding in Thermus thermophilus isopropylmalate dehydrogenase
Author(s) -
Zhang Tao,
Koshland Daniel E.
Publication year - 1995
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560040111
Subject(s) - thermus thermophilus , cofactor , isocitrate dehydrogenase , homology modeling , nad+ kinase , biochemistry , substrate (aquarium) , binding site , dehydrogenase , active site , biology , enzyme , chemistry , stereochemistry , escherichia coli , ecology , gene
The Thermus thermophilus 3‐isopropylmalate dehydrogenase (IPMDH) and Escherichia coli isocitrate dehydrogenase (ICDH) are two functionally and evolutionarily related enzymes with distinct substrate specificities. To understand the determinants of substrate specificities of the two proteins, the substrate and coenzyme in IPMDH were docked into their respective binding sites based on the published structure for apo IPMDH and its sequence and structural homology to ICDH. This modeling study suggests that (1) the substrate and coenzyme (NAD) binding modes of IPMDH are significantly different from those of ICDH, (2) the interactions between the substrates and coenzymes help explain the differences in substrate specificities of IPMDH and ICDH, and (3) binding of the substrate and coenzyme should induce a conformational change in the structure of IPMDH.