This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1k75
From Proteopedia
| |||||||
| , resolution 1.75Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | hisD (Escherichia coli) | ||||||
| Activity: | Histidinol dehydrogenase, with EC number 1.1.1.23 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
Page seeded by OCA on Sun Mar 30 21:44:20 2008
Categories: Escherichia coli | Histidinol dehydrogenase | Single protein | BSGI, Montreal-Kingston Bacterial Structural Genomics Initiative. | Barbosa, J A.R G. | Cygler, M. | Larocque, R. | Li, Y. | Matte, A. | Schrag, J. | Sivaraman, J. | 4 domain | Bsgi | Hisd | Homodimer | L-histidine biosynthesis | L-histidinol dehydrogenase | Montreal-kingston bacterial structural genomics initiative | Nad cofactor | Rossman fold | Structural genomic | Zinc
