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Oxidoreductase PDB id
Protein chains
431 a.a. *
HSM ×2
_ZN ×2
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: L-histidinol dehydrogenase (hisd) structure complexed with h (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)
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.Schr 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
02-Nov-01     Release date:   12-Jun-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P06988  (HISX_ECOLI) -  Histidinol dehydrogenase
434 a.a.
431 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Histidinol dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Histidine Biosynthesis (late stages)
      Reaction: L-histidinol + H2O + 2 NAD+ = L-histidine + 2 NADH
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 
  GO annot!
  Biological process     metabolic process   4 terms 
  Biochemical function     oxidoreductase activity     6 terms  


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.
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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21461427 M.R.Abdo, P.Joseph, J.Mortier, F.Turtaut, J.L.Montero, B.Masereel, S.Köhler, and J.Y.Winum (2011).
Anti-virulence strategy against Brucella suis: synthesis, biological evaluation and molecular modeling of selective histidinol dehydrogenase inhibitors.
  Org Biomol Chem, 9, 3681-3690.  
20976204 C.H.Chu, W.C.Lo, H.W.Wang, Y.C.Hsu, J.K.Hwang, P.C.Lyu, T.W.Pai, and C.Y.Tang (2010).
Detection and alignment of 3D domain swapping proteins using angle-distance image-based secondary structural matching techniques.
  PLoS One, 5, e13361.  
19891608 P.Ferreira, A.Hernández-Ortega, B.Herguedas, J.Rencoret, A.Gutiérrez, M.J.Martínez, J.Jiménez-Barbero, M.Medina, and A.T.Martínez (2010).
Kinetic and chemical characterization of aldehyde oxidation by fungal aryl-alcohol oxidase.
  Biochem J, 425, 585-593.  
20116858 X.Li, S.A.Hayik, and K.M.Merz (2010).
QM/MM X-ray refinement of zinc metalloenzymes.
  J Inorg Biochem, 104, 512-522.  
17632581 C.L.Wang, A.Malkus, S.M.Zuzga, P.F.Chang, B.M.Cunfer, E.Arseniuk, and P.P.Ueng (2007).
Diversity of the trifunctional histidine biosynthesis gene (his) in cereal Phaeosphaeria species.
  Genome, 50, 595-609.  
12837772 A.Matte, J.Sivaraman, I.Ekiel, K.Gehring, Z.Jia, and M.Cygler (2003).
Contribution of structural genomics to understanding the biology of Escherichia coli.
  J Bacteriol, 185, 3994-4002.  
14690428 M.Ghanem, F.Fan, K.Francis, and G.Gadda (2003).
Spectroscopic and kinetic properties of recombinant choline oxidase from Arthrobacter globiformis.
  Biochemistry, 42, 15179-15188.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.