1K75: The L-histidinol Dehydrogenase (hisd) Structure Implicates Domain Swapping And Gene Duplication

Citation:
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 ) 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.
PDB ID: 1K75Download
MMDB ID: 18929
PDB Deposition Date: 2001/10/18
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 1.75  Å
Source Organism:
Similar Structures:
Biological Unit for 1K75: dimeric; determined by author and by software (PISA)
Molecular Components in 1K75
Label Count Molecule
Proteins (2 molecules)
2
L-histidinol Dehydrogenase(Gene symbol: hisD)
Molecule annotation
Chemicals (5 molecules)
1
4
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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