PDBsum entry: 1kar

Oxidoreductase

PDB id: 1kar

Contents

Protein chains

431 a.a. *

Ligands

HSM ×2

Metals

_ZN ×2

* Residue conservation analysis

PDB id:

1kar

Name:

Oxidoreductase

Title:

L-histidinol dehydrogenase (hisd) structure complexed with histamine (inhibitor), zinc and NAD (cofactor)

Structure:

Histidinol dehydrogenase. Chain: a, b. Synonym: hdh. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: hisd. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.10Å R-factor: 0.248 R-free: 0.281

Authors:

J.A.R.G.Barbosa,J.Sivaraman,Y.Li,R.Larocque,A.Matte, J.D.Schrag,M.Cygler

Key ref:

J.A.Barbosa et al. (2002). Mechanism of action and NAD+-binding mode revealed by the crystal structure of L-histidinol dehydrogenase. Proc Natl Acad Sci U S A, 99, 1859-1864. PubMed id: 11842181 DOI: 10.1073/pnas.022476199

Date:

02-Nov-01 Release date: 12-Jun-02

Protein chains

P06988  (HISX_ECOLI) -  Histidinol dehydrogenase

Seq: 434 a.a.

Struc: 431 a.a.

Enzyme reactions

• Enzyme class: E.C.1.1.1.23 - Histidinol dehydrogenase.
• Pathway: Histidine Biosynthesis (late stages)
• Reaction: L-histidinol + H₂O + 2 NAD⁺ = L-histidine + 2 NADH

L-histidinol (Bound ligand (Het Group name = HSM) matches with 80.00% similarity) + H(2)O + 2 × NAD(+) = L-histidine + 2 × NADH

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biological process: metabolic process (4 terms)
• Biochemical function: oxidoreductase activity (5 terms)

reference

DOI no: 10.1073/pnas.022476199

Proc Natl Acad Sci U S A 99:1859-1864 (2002)

PubMed id: 11842181

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

J.A.Barbosa, J.Sivaraman, Y.Li, R.Larocque, A.Matte, J.D.Schrag, M.Cygler.

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.

Selected figure(s)

Figure 1.
Fig. 1. Reactions catalyzed by HisD (after ref. 14). The structure allowed identification of residues Glu-326 as being base B2 and His-327 as B1, B3, and B4. Glu-326 is responsible for the activation of a water molecule that will attack the reactive carbon in step 2 of the reaction mechanism.

Figure 2.
Fig. 2. Structure and topology of HisD. (A) Stereo view of the monomer. Domains: 1, blue; 2, green; 3, orange; 4, magenta. L-histidinol, NAD^+, and the Zn2+ are shown as ball-and-sticks. (B) Domain 1. Rossmann fold shown in blue, V-shaped pairs of helices (residues 25-103) connected by a linker that forms the sixth strand are in cyan. (C) Domain 2. Rossmann fold (green) in similar orientation as B. Strand-helix hairpin completes the -sheet (residues 1-24, magenta). (D) Topology diagram. Secondary structure elements are numbered consecutively. The chain meanders between domains in the order 2-1-3-1-2-1-3-4. (E) HisD dimer with one molecule colored as in A and the other shown in pale colors. Zn2+ atoms and NAD^+ bound to each monomer (red) define the position of the active site. Prepared with MOLSCRIPT (46) and RASTER3D (47).

Figures were selected by an automated process.