1yon
From Proteopedia
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| , resolution 1.95Å | |||||||
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| Ligands: | |||||||
| Gene: | panE (Escherichia coli) | ||||||
| Activity: | 2-dehydropantoate 2-reductase, with EC number 1.1.1.169 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Escherichia coli ketopantoate reductase in complex with 2-monophosphoadenosine-5'-diphosphate
Overview
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.
About this Structure
1YON is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
pH-tuneable binding of 2'-phospho-ADP-ribose to ketopantoate reductase: a structural and calorimetric study., Ciulli A, Lobley CM, Tuck KL, Smith AG, Blundell TL, Abell C, Acta Crystallogr D Biol Crystallogr. 2007 Feb;63(Pt 2):171-8. Epub 2007, Jan 16. PMID:17242510
Page seeded by OCA on Thu Mar 20 15:25:33 2008
Categories: 2-dehydropantoate 2-reductase | Escherichia coli | Single protein | Abell, C. | Blundell, T L. | Ciulli, A. | Lobley, C M.C. | Smith, A G. | Tuck, K L. | Williams, G. | APX | 2'-monophosphoadenosine-5'-diphosphate | Ketopantoate | Nadp+ dependent | Pantothenate pathway | Secondary alcohol dehydrogenase
