In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 4 ( 2002-02-19), p. 1859-1864
Abstract:
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 1.1.1.23 ) 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 Å). 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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.022476199
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2002
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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