PDBsum entry: 1nsk

Phosphotransferase (po4 as acceptor)

PDB id: 1nsk

Contents

Protein chains

(+ 0 more) 151 a.a. *

* Residue conservation analysis

PDB id:

1nsk

Name:

Phosphotransferase (po4 as acceptor)

Title:

The crystal structure of a human nucleoside diphosphate kinase, nm23-h2

Structure:

Nucleoside diphosphate kinase. Chain: r, l, t, u, n, o. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nm23-h2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Hexamer (from PQS)

Resolution:

2.80Å R-factor: 0.249 R-free: 0.294

Authors:

R.L.Williams,O.Perisic

Key ref:

P.A.Webb et al. (1995). The crystal structure of a human nucleoside diphosphate kinase, NM23-H2. J Mol Biol, 251, 574-587. PubMed id: 7658474 DOI: 10.1006/jmbi.1995.0457

Date:

04-Jul-95 Release date: 15-Oct-95

Protein chains

P22392  (NDKB_HUMAN) -  Nucleoside diphosphate kinase B

Seq: 152 a.a.

Struc: 151 a.a.

Enzyme reactions

• Enzyme class 2: E.C.2.7.13.3 - Histidine kinase.
• Reaction: ATP + protein L-histidine = ADP + protein N-phospho-L-histidine
• Enzyme class 3: E.C.2.7.4.6 - Nucleoside-diphosphate kinase.
• Reaction: ATP + nucleoside diphosphate = ADP + nucleoside triphosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

 Gene Ontology (GO) functional annotation 

• Cellular component: ruffle (5 terms)
• Biological process: cell adhesion (18 terms)
• Biochemical function: nucleotide binding (9 terms)

reference

DOI no: 10.1006/jmbi.1995.0457

J Mol Biol 251:574-587 (1995)

PubMed id: 7658474

The crystal structure of a human nucleoside diphosphate kinase, NM23-H2.

P.A.Webb, O.Perisic, C.E.Mendola, J.M.Backer, R.L.Williams.

ABSTRACT

The 2.8 A resolution X-ray structure of NM23-H2 has been determined by molecular replacement using the structure of Myxococcus xanthus nucleoside diphosphate (NDP) kinase. NM23-H2 is a human NDP kinase. The enzyme catalyses phosphoryl transfer, binds DNA, and can activate the transcription of the c-myc oncogene in vitro. NM23 has also been reported to be a suppressor of metastasis in some types of tumours. Whereas the M. xanthus NDP kinase is a tetramer, NM23-H2 is a hexamer. The fold of NM23-H2 is identical to the fold of other NDP kinases. Two antiparallel helices joined by a turn form one edge of the nucleotide binding cleft. This region moves in a hinge-like fashion in response to substrate binding and crystal packing forces. Additional differences in conformation among the NDP kinases are principally in regions involved in protein-protein contacts within the oligomers. The only protein-protein interaction conserved among all NDP kinases is a dimeric interaction. Several mutations of NM23-H2 have been detected in tumour tissues. These mutations do not involve residues interacting with the substrates, and probably destabilise the enzyme without directly affecting the catalytic activity. Low level phosphorylation of serines has been reported for NM23 both in vitro and in vivo. The structure of the hexamer indicates that two serine residues that have been reported as being phosphorylated, Ser44 and Ser122, are on the surface of the hexamer, and are likely to be phosphorylated by exogenous kinases. In contrast, Ser120 is buried, and is most likely phosphorylated by a direct transfer from the phosphohistidine intermediate of the reaction mechanism.

Selected figure(s)

Figure 4.
Figure 4. The NM23-H2 hexamer that is present in the asymmetric unit. The hexamer is formed from three dimers. Two dimers (cyan and yellow) in a hexamer are shown in a ribbon representation, and one dimer is shown as a space filling model. The catalytic His118 (shown in magenta by ball-and-stick representation) marks the active site of the enzyme, and the C termini are coloured blue. The residue that is likely to form intermolecular disulphide bonds under non-reducing conditions, Cys145, is shown in the centre of the image. The green Cys145 is part of the upper molecule of the cyan dimer, and the red Cys145 is part of the lower molecule of the yellow dimer.

Figure 8.
Figure 8. Molecular surface of the NM23-H2 hexamer. The five residues that are basic in NM23-H2, but which are neutral or acidic in the NM23-H1 sequence (which is 88% identical), are coloured blue. This diagram was drawn with GRASP.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1995, 251, 574-587) copyright 1995.

Figures were selected by an automated process.