PDBsum entry 1dhs

Transferase

PDB id: 1dhs

Contents

Protein chain

344 a.a. *

Ligands

NAD

Waters ×267

* Residue conservation analysis

PDB id:

1dhs

Name:

Transferase

Title:

Crystal structure of the NAD complex of human deoxyhypusine synthase

Structure:

Deoxyhypusine synthase. Chain: a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: hela cells. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Tetramer (from PDB file)

Resolution:

2.20Å R-factor: 0.153 R-free: 0.242

Authors:

D.-I.Liao,D.R.Davies

Key ref:

D.I.Liao et al. (1998). Crystal structure of the NAD complex of human deoxyhypusine synthase: an enzyme with a ball-and-chain mechanism for blocking the active site. Structure, 6, 23-32. PubMed id: 9493264 DOI: 10.1016/S0969-2126(98)00004-5

Date:

28-Oct-97 Release date: 25-Feb-98

Protein chain

P49366  (DHYS_HUMAN) -  Deoxyhypusine synthase from Homo sapiens

Seq: 369 a.a.

Struc: 344 a.a.

Enzyme reactions

• Enzyme class: E.C.2.5.1.46 - deoxyhypusine synthase.
• Pathway: EC 2.5.1.46
• Reaction: [eIF5A protein]-L-lysine + spermidine = [eIF5A protein]-deoxyhypusine + propane-1,3-diamine
• Cofactor: NAD(+)

NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/S0969-2126(98)00004-5

Structure 6:23-32 (1998)

PubMed id: 9493264

Crystal structure of the NAD complex of human deoxyhypusine synthase: an enzyme with a ball-and-chain mechanism for blocking the active site.

D.I.Liao, E.C.Wolff, M.H.Park, D.R.Davies.

ABSTRACT

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.

Selected figure(s)

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.

The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 23-32) copyright 1998.

Figure was selected by an automated process.