2.0 Å X‐ray structure of the ternary complex of 7,8‐dihydro‐6‐hydroxymethylpterinpyrophosphokinase from Escherichia coli with ATP and a substrate analogue

FEBS Letters

Achari, Aniruddha¹  Somers, Donald O'N¹  Scott, David L¹  Champness, John N¹  Bryant, Patrick K¹  Rosemond, Jane¹  Stammers, David K¹ 

[1] Glaxo Wellcome R&D, Medicines Research Centre, Gunnell's Wood Road, Stevenage SG1 2NY, UK

关键词: Anti-microbial;    Folate pathway;    Drug target;    X-ray crystallography;    7;    8-Dihydro-6-hydroxymethylpterinpyrophosphokinase;    PPPK;    7;    8-dihydro-6-hydroxymethylpterinpyrophosphokinase;    HP;    7;    8-dihydro-6-hydroxymethylpterin;    DHPS;    dihydropteroate synthase;    NDP;    nucleoside diphosphate;   

DOI  :  10.1016/S0014-5793(99)00860-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The X-ray crystal structure of 7,8-dihydro-6-hydroxymethylpterinpyrophosphokinase (PPPK) in a ternary complex with ATP and a pterin analogue has been solved to 2.0 Å resolution, giving, for the first time, detailed information of the PPPK/ATP intermolecular interactions and the accompanying conformational change. The first 100 residues of the 158 residue peptide contain a βαββαβ motif present in several other proteins including nucleoside diphosphate kinase. Comparative sequence examination of a wide range of prokaryotic and lower eukaryotic species confirms the conservation of the PPPK active site, indicating the value of this de novo folate biosynthesis pathway enzyme as a potential target for the development of novel broad-spectrum anti-infective agents.

【 授权许可】

Unknown