1YON

Escherichia coli ketopantoate reductase in complex with 2-monophosphoadenosine-5'-diphosphate

Summary for 1YON

• Entry DOI: 10.2210/pdb1yon/pdb
• Related: 1KS9 1YJQ
• Descriptor: 2-dehydropantoate 2-reductase, [(2R,3R,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3-HYDROXY-4-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]METHYL [(2R,3S,4R,5R)-3,4,5-TRIHYDROXYTETRAHYDROFURAN-2-YL]METHYL DIHYDROGEN DIPHOSPHATE (3 entities in total)
• Functional Keywords: ketopantoate, nadp+ dependent, 2'-monophosphoadenosine-5'-diphosphate, pantothenate pathway, secondary alcohol dehydrogenase, oxidoreductase
• Biological source: Escherichia coli
• Cellular location: Cytoplasm : P0A9J4
• Total number of polymer chains: 1
• Total formula weight: 34547.00

Authors

Ciulli, A.,Lobley, C.M.C.,Tuck, K.L.,Williams, G.,Smith, A.G.,Blundell, T.L.,Abell, C. (deposition date: 2005-01-28, release date: 2006-04-18, Last modification date: 2024-11-13)

Primary citation

Ciulli, A.,Lobley, C.M.,Tuck, K.L.,Smith, A.G.,Blundell, T.L.,Abell, C.
pH-tuneable binding of 2'-phospho-ADP-ribose to ketopantoate reductase: a structural and calorimetric study.
Acta Crystallogr.,Sect.D, 63:171-178, 2007

PubMed Abstract: The crystal structure of Escherichia coli ketopantoate reductase in complex with 2'-monophosphoadenosine 5'-diphosphoribose, a fragment of NADP+ that lacks the nicotinamide ring, is reported. The ligand is bound at the enzyme active site in the opposite orientation to that observed for NADP+, with the adenine ring occupying the lipophilic nicotinamide pocket. Isothermal titration calorimetry with R31A and N98A mutants of the enzyme is used to show that the unusual ;reversed binding mode' observed in the crystal is triggered by changes in the protonation of binding groups at low pH. This research has important implications for fragment-based approaches to drug design, namely that the crystallization conditions and the chemical modification of ligands can have unexpected effects on the binding modes.

PubMed: 17242510
DOI: 10.1107/S0907444906044465

Experimental method

X-RAY DIFFRACTION (1.95 Å)