1K75

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

Summary for 1K75

• Entry DOI: 10.2210/pdb1k75/pdb
• Descriptor: L-histidinol dehydrogenase, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: l-histidinol dehydrogenase, homodimer, rossmann fold, 4 domains, hisd, l-histidine biosynthesis, nad cofactor, montreal-kingston bacterial structural genomics initiative, bsgi, structural genomics, oxidoreductase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 93345.39

Authors

Barbosa, J.A.R.G.,Sivaraman, J.,Li, Y.,Larocque, R.,Matte, A.,Schrag, J.,Cygler, M.,Montreal-Kingston Bacterial Structural Genomics Initiative (BSGI) (deposition date: 2001-10-18, release date: 2002-02-27, Last modification date: 2024-11-06)

Primary citation

Barbosa, J.A.R.G.,Sivaraman, J.,Li, Y.,Larocque, R.,Matte, A.,Schrag, J.D.,Cygler, M.
Mechanism of action and NAD+-binding mode revealed by the crystal structure of L-histidinol dehydrogenase.
Proc.Natl.Acad.Sci.USA, 99:1859-1864, 2002

PubMed 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.

PubMed: 11842181
DOI: 10.1073/pnas.022476199

Experimental method

X-RAY DIFFRACTION (1.75 Å)