1KAR

L-HISTIDINOL DEHYDROGENASE (HISD) STRUCTURE COMPLEXED WITH HISTAMINE (INHIBITOR), ZINC AND NAD (COFACTOR)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.281 
  • R-Value Work: 0.248 
  • R-Value Observed: 0.248 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

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

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

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

  • DOI: https://doi.org/10.1073/pnas.022476199
  • Primary Citation of Related Structures:  
    1K75, 1KAE, 1KAH, 1KAR

  • 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.


  • Organizational Affiliation

    Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montreal, QC, Canada H4P 2R2.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Histidinol dehydrogenase
A, B
434Escherichia coliMutation(s): 7 
Gene Names: HISD
EC: 1.1.1.23
UniProt
Find proteins for P06988 (Escherichia coli (strain K12))
Explore P06988 
Go to UniProtKB:  P06988
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06988
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A, B
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.281 
  • R-Value Work: 0.248 
  • R-Value Observed: 0.248 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.34α = 90
b = 109.04β = 90
c = 157.94γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-06-12
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2014-11-12
    Changes: Structure summary
  • Version 1.4: 2023-08-16
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.5: 2023-11-15
    Changes: Data collection