1a05
From Proteopedia
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CRYSTAL STRUCTURE OF THE COMPLEX OF 3-ISOPROPYLMALATE DEHYDROGENASE FROM THIOBACILLUS FERROOXIDANS WITH 3-ISOPROPYLMALATE
Overview
BACKGROUND: 3-Isopropylmalate dehydrogenase (IPMDH) and isocitrate, dehydrogenase (ICDH) belong to a unique family of bifunctional, decarboxylating dehydrogenases. Although the ICDH dimer catalyzes its, reaction under a closed conformation, known structures of the IPMDH dimer, (without substrate) adopt a fully open or a partially closed form., Considering the similarity in the catalytic mechanism, the IPMDH dimer, must be in a fully closed conformation during the reaction. A large, conformational change should therefore occur upon substrate binding., RESULTS: We have determined the crystal structure of IPMDH from, Thiobacillus ferrooxidans (Tf) complexed with 3-isopropylmalate (IPM) at, 2.0 A resolution by the molecular replacement method. The structure shows, a fully closed conformation and the substrate-binding site is quite, similar to that of ICDH except for a region around the gamma-isopropyl, group. The gamma group is recognized by a unique hydrophobic pocket, which, includes Glu88, Leu91 and Leu92 from subunit 1 and Val193' from subunit 2., CONCLUSIONS: A large movement of domain 1 is induced by substrate binding, which results in the formation of the hydrophobic pocket for the, gamma-isopropyl moiety of IPM. A glutamic acid in domain 1, Glu88, participates in the formation of the hydrophobic pocket. The C beta and C, gamma atoms of Glu88 interact with the gamma-isopropyl moiety of IPM and, are central to the recognition of substrate. The acidic tip of Glu88 is, likely to interact with the nicotinamide mononucleotide (NMN) ribose of, NAD+ in the ternary complex. This structure clearly explains the substrate, specificity of IPMDH.
About this Structure
1A05 is a Single protein structure of sequence from Acidithiobacillus ferrooxidans with MG and IPM as ligands. Active as 3-isopropylmalate dehydrogenase, with EC number 1.1.1.85 Full crystallographic information is available from OCA.
Reference
Structure of 3-isopropylmalate dehydrogenase in complex with 3-isopropylmalate at 2.0 A resolution: the role of Glu88 in the unique substrate-recognition mechanism., Imada K, Inagaki K, Matsunami H, Kawaguchi H, Tanaka H, Tanaka N, Namba K, Structure. 1998 Aug 15;6(8):971-82. PMID:9739088
Page seeded by OCA on Tue Nov 20 10:31:37 2007
