1dhs

CRYSTAL STRUCTURE OF THE NAD COMPLEX OF HUMAN DEOXYHYPUSINE SYNTHASE

spinqualitylabelsall models 1dhs, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1dhs is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAD Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Crystal structure of the NAD complex of human deoxyhypusine synthase: an enzyme with a ball-and-chain mechanism for blocking the active site.,Liao DI, Wolff EC, Park MH, Davies DR Structure. 1998 Jan 15;6(1):23-32. PMID:9493264 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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