1DHS: Crystal Structure Of The Nad Complex Of Human Deoxyhypusine Synthase

BACKGROUND: Eukaryotic initiation factor 5A (elF-5A) contains an unusual amino acid, hypusine [N epsilon-(4-aminobutyl-2-hydroxy)lysine]. The first step in the post-translational formation of hypusine is catalysed by the enzyme deoxyhypusine synthase (DHS). The modified version of elF-5A, and DHS, are required for eukaryotic cell proliferation. Knowledge of the three-dimensional structure of this key enzyme should permit the design of specific inhibitors that may be useful as anti-proliferative agents. RESULTS: The crystal structure of human DHS with bound NAD cofactor has been determined and refined at 2.2 A resolution. The enzyme is a tetramer of four identical subunits arranged with 222 symmetry; each subunit contains a nucleotide-binding (or Rossmann) fold. The tetramer comprises two tightly associated dimers and contains four active sites, two in each dimer interface. The catalytic portion of each active site is located in one subunit while the NAD-binding site is located in the other. The entrance to the active-site cavity is blocked by a two-turn alpha helix, part of a third subunit, to which it is joined by an extended loop. CONCLUSIONS: The active site of DHS is a cavity buried below the surface of the enzyme at the interface between two subunits. In the conformation observed here, the substrate-binding site is inaccessible and we propose that the reaction steps carried out by the enzyme must be accompanied by significant conformational changes, the least of which would be the displacement of the two-turn alpha helix.
PDB ID: 1DHSDownload
MMDB ID: 48658
PDB Deposition Date: 1997/10/28
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 1DHS: tetrameric; determined by author and by software (PISA,PQS)
Molecular Components in 1DHS
Label Count Molecule
Proteins (4 molecules)
Deoxyhypusine Synthase(Gene symbol: DHPS)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB