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

• Published in: FEBS letters 1999-07, Vol.456 (1), p.49-53
• Main Authors: Stammers, David K, Achari, Aniruddha, Somers, Donald O’N, Bryant, Patrick K, Rosemond, Jane, Scott, David L, Champness, John N
• Format: Article
• Language: English
• Subjects: 7,8-Dihydro-6-hydroxymethylpterinpyrophosphokinase; Adenosine Triphosphate - chemistry; Adenosine Triphosphate - metabolism; Amino Acid Sequence; Anti-microbial; Binding Sites; Conserved Sequence; Crystallography, X-Ray; DHPS, dihydropteroate synthase; Dihydropteroate Synthase - chemistry; Dihydropteroate Synthase - metabolism; Diphosphotransferases - chemistry; Diphosphotransferases - metabolism; Drug target; Escherichia coli - enzymology; Folate pathway; HP, 7,8-dihydro-6-hydroxymethylpterin; Models, Molecular; NDP, nucleoside diphosphate; PPPK, 7,8-dihydro-6-hydroxymethylpterinpyrophosphokinase; Protein Conformation; Protein Folding; Pterins - chemistry; Pterins - metabolism; X-ray crystallography
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)00860-1

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.