1i9a

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spinqualitylabelsall models 1i9a, resolution 2.5Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

STRUCTURAL STUDIES OF CHOLESTEROL BIOSYNTHESIS: MEVALONATE 5-DIPHOSPHATE DECARBOXYLASE AND ISOPENTENYL DIPHOSPHATE ISOMERASE

Overview

X-ray structures of two enzymes in the sterol/isoprenoid biosynthesis, pathway have been determined in a structural genomics pilot study., Mevalonate-5-diphosphate decarboxylase (MDD) is a single-domain alpha/beta, protein that catalyzes the last of three sequential ATP-dependent, reactions which convert mevalonate to isopentenyl diphosphate. Isopentenyl, disphosphate isomerase (IDI) is an alpha/beta metalloenzyme that catalyzes, interconversion of isopentenyl diphosphate and dimethylallyl diphosphate, which condense in the next step toward synthesis of sterols and a host of, natural products. Homology modeling of related proteins and comparisons of, the MDD and IDI structures with two other experimentally determined, structures have shown that MDD is a member of the GHMP superfamily of, small-molecule kinases and IDI is similar to the nudix hydrolases, which, act on nucleotide diphosphatecontaining substrates. Structural models were, produced for 379 proteins, encompassing a substantial fraction of both, protein superfamilies. All three enzymes responsible for synthesis of, isopentenyl diphosphate from mevalonate (mevalonate kinase, phosphomevalonate kinase, and MDD) share the same fold, catalyze, phosphorylation of chemically similar substrates (MDD decarboxylation, involves phosphorylation of mevalonate diphosphate), and seem to have, evolved from a common ancestor. These structures and the structural models, derived from them provide a framework for interpreting biochemical, function and evolutionary relationships.

About this Structure

1I9A is a Single protein structure of sequence from Escherichia coli with MN as ligand. Active as Isopentenyl-diphosphate Delta-isomerase, with EC number 5.3.3.2 Full crystallographic information is available from OCA.

Reference

Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis., Bonanno JB, Edo C, Eswar N, Pieper U, Romanowski MJ, Ilyin V, Gerchman SE, Kycia H, Studier FW, Sali A, Burley SK, Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):12896-901. PMID:11698677

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