1k75

From Proteopedia

Revision as of 16:47, 20 November 2007

The L-histidinol dehydrogenase (hisD) structure implicates domain swapping and gene duplication.

Overview

The histidine biosynthetic pathway is an ancient one found in bacteria, archaebacteria, fungi, and plants that converts 5-phosphoribosyl, 1-pyrophosphate to l-histidine in 10 enzymatic reactions. This pathway, provided a paradigm for the operon, transcriptional regulation of gene, expression, and feedback inhibition of a pathway. l-histidinol, dehydrogenase (HisD, EC ) catalyzes the last two steps in the biosynthesis, of l-histidine: sequential NAD-dependent oxidations of l-histidinol to, l-histidinaldehyde and then to l-histidine. HisD functions as a homodimer, and requires the presence of one Zn(2+) cation per monomer. We have, determined the three-dimensional structure of Escherichia coli HisD in the, apo state as well as complexes with substrate, Zn(2+), and NAD(+) (best, resolution is 1.7 A). Each monomer is made of four domains, whereas the, intertwined dimer possibly results from domain swapping. Two domains, display a very similar incomplete Rossmann fold that suggests an ancient, event of gene duplication. Residues from both monomers form the active, site. Zn(2+) plays a crucial role in substrate binding but is not directly, involved in catalysis. The active site residue His-327 participates in, acid-base catalysis, whereas Glu-326 activates a water molecule. NAD(+), binds weakly to one of the Rossmann fold domains in a manner different, from that previously observed for other proteins having a Rossmann fold.

About this Structure

1K75 is a Single protein structure of sequence from Escherichia coli with SO4 and GOL as ligands. Active as Histidinol dehydrogenase, with EC number 1.1.1.23 Full crystallographic information is available from OCA.

Reference

Mechanism of action and NAD+-binding mode revealed by the crystal structure of L-histidinol dehydrogenase., Barbosa JA, Sivaraman J, Li Y, Larocque R, Matte A, Schrag JD, Cygler M, Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1859-64. Epub 2002 Feb 12. PMID:11842181

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