PDBsum entry 3elh

Transferase

PDB id: 3elh

Contents

Protein chains

(+ 0 more) 133 a.a. *

Ligands

DUD ×6

Metals

_MG ×6

Waters ×151

* Residue conservation analysis

PDB id:

3elh

Name:

Transferase

Title:

X-ray structure of acanthamoeba ployphaga mimivirus nucleoside diphosphate kinase complexed with dudp

Structure:

Nucleoside diphosphate kinase. Chain: a, b, c, d, e, f. Synonym: ndp kinase, ndk. Engineered: yes

Source:

Acanthamoeba polyphaga mimivirus. Organism_taxid: 212035. Gene: mimi_r418, ndk. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.40Å R-factor: 0.195 R-free: 0.231

Authors:

S.Jeudy,A.Lartigue,J.M.Claverie,C.Abergel

Key ref:

S.Jeudy et al. (2009). Dissecting the unique nucleotide specificity of mimivirus nucleoside diphosphate kinase. J Virol, 83, 7142-7150. PubMed id: 19439473

Date:

22-Sep-08 Release date: 16-Jun-09

Protein chains

Q5UQL3  (NDK_MIMIV) -  Nucleoside diphosphate kinase from Acanthamoeba polyphaga mimivirus

Seq: 137 a.a.

Struc: 133 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.4.6 - nucleoside-diphosphate kinase.
• Reaction:
  1. a ribonucleoside 5'-diphosphate + ATP = a ribonucleoside 5'-triphosphate + ADP
  2. a 2'-deoxyribonucleoside 5'-diphosphate + ATP = a 2'-deoxyribonucleoside 5'-triphosphate + ADP

ribonucleoside 5'-diphosphate + ATP = ribonucleoside 5'-triphosphate + ADP (Bound ligand (Het Group name = DUD) matches with 75.86% similarity)

2'-deoxyribonucleoside 5'-diphosphate + ATP = 2'-deoxyribonucleoside 5'-triphosphate + ADP (Bound ligand (Het Group name = DUD) matches with 75.86% similarity)

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

reference

J Virol 83:7142-7150 (2009)

PubMed id: 19439473

Dissecting the unique nucleotide specificity of mimivirus nucleoside diphosphate kinase.

S.Jeudy, A.Lartigue, J.M.Claverie, C.Abergel.

ABSTRACT

The analysis of the Acanthamoeba polyphaga mimivirus genome revealed the first virus-encoded nucleoside diphosphate kinase (NDK), an enzyme that is central to the synthesis of RNA and DNA, ubiquitous in cellular organisms, and well conserved among the three domains of life. In contrast with the broad specificity of cellular NDKs for all types of ribo- and deoxyribonucleotides, the mimivirus enzyme exhibits a strongly preferential affinity for deoxypyrimidines. In order to elucidate the molecular basis of this unique substrate specificity, we determined the three-dimensional (3D) structure of the Acanthamoeba polyphaga mimivirus NDK alone and in complex with various nucleotides. As predicted from a sequence comparison with cellular NDKs, the 3D structure of the mimivirus enzyme exhibits a shorter Kpn loop, previously recognized as a main feature of the NDK active site. The structure of the viral enzyme in complex with various nucleotides also pinpointed two residue changes, both located near the active site and specific to the viral NDK, which could explain its stronger affinity for deoxynucleotides and pyrimidine nucleotides. The role of these residues was explored by building a set of viral NDK variants, assaying their enzymatic activities, and determining their 3D structures in complex with various nucleotides. A total of 26 crystallographic structures were determined at resolutions ranging from 2.8 A to 1.5 A. Our results suggest that the mimivirus enzyme progressively evolved from an ancestral NDK under the constraints of optimizing its efficiency for the replication of an AT-rich (73%) viral genome in a thymidine-limited host environment.