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PDBsum entry 1dhs
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the NAD complex of human deoxyhypusine synthase: an enzyme with a ball-And-Chain mechanism for blocking the active site.
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Authors
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D.I.Liao,
E.C.Wolff,
M.H.Park,
D.R.Davies.
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Ref.
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Structure, 1998,
6,
23-32.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
89%.
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Abstract
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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.
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Figure 4.
Figure 4. A ball-and-stick model of the DHS active-site
structure. The N-terminal helix from a third monomer that covers
the pocket entrance is in pale yellow. The orientation and color
scheme of this figure are the same as in Figure 2. For clarity,
only the nicotinamide ring and its adjacent ribose of NAD are
shown. The hydrogen bonds between water molecules and sidechains
of the protein residues are indicated by gray dotted lines;
atoms are shown in standard colours. The N-terminal helix from
the third monomer blocks the access to the active site.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1998,
6,
23-32)
copyright 1998.
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