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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 A 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 betaalpha betabeta alphabeta 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.

Type

Journal article

Journal

FEBS Lett

Publication Date

30/07/1999

Volume

456

Pages

49 - 53

Keywords

Adenosine Triphosphate, Amino Acid Sequence, Binding Sites, Conserved Sequence, Crystallography, X-Ray, Dihydropteroate Synthase, Diphosphotransferases, Escherichia coli, Models, Molecular, Protein Conformation, Protein Folding, Pterins