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L-HISTIDINOL DEHYDROGENASE (HISD) STRUCTURE COMPLEXED WITH L-HISTIDINOL (SUBSTRATE), ZINC AND NAD (COFACTOR)L-HISTIDINOL DEHYDROGENASE (HISD) STRUCTURE COMPLEXED WITH L-HISTIDINOL (SUBSTRATE), ZINC AND NAD (COFACTOR)
Structural highlights
FunctionHISX_ECOLI Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine.[HAMAP-Rule:MF_01024] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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