Unknown

Dataset Information

0

Mechanism of action and NAD+-binding mode revealed by the crystal structure of L-histidinol dehydrogenase.


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.

SUBMITTER: Barbosa JA 

PROVIDER: S-EPMC122284 | biostudies-literature | 2002 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Mechanism of action and NAD+-binding mode revealed by the crystal structure of L-histidinol dehydrogenase.

Barbosa João A R G JA   Sivaraman J J   Li Yunge Y   Larocque Robert R   Matte Allan A   Schrag Joseph D JD   Cygler Miroslaw M  

Proceedings of the National Academy of Sciences of the United States of America 20020212 4


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-histidinal  ...[more]

Similar Datasets

| S-EPMC164887 | biostudies-literature
| S-EPMC2832993 | biostudies-literature
| S-EPMC5585171 | biostudies-literature
| S-EPMC5069622 | biostudies-literature
| S-EPMC1851648 | biostudies-literature
| S-EPMC2676054 | biostudies-literature
| S-EPMC1161136 | biostudies-other
| S-EPMC1262676 | biostudies-literature
| S-EPMC2951230 | biostudies-literature
| S-EPMC11199699 | biostudies-literature