1yon
From Proteopedia
(New page: 200px<br /><applet load="1yon" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yon, resolution 1.95Å" /> '''Escherichia coli ket...) |
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| - | [[Image:1yon.gif|left|200px]]<br /><applet load="1yon" size=" | + | [[Image:1yon.gif|left|200px]]<br /><applet load="1yon" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1yon, resolution 1.95Å" /> | caption="1yon, resolution 1.95Å" /> | ||
'''Escherichia coli ketopantoate reductase in complex with 2-monophosphoadenosine-5'-diphosphate'''<br /> | '''Escherichia coli ketopantoate reductase in complex with 2-monophosphoadenosine-5'-diphosphate'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of Escherichia coli ketopantoate reductase in | + | 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== | ==About this Structure== | ||
| - | 1YON is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with APX as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/2-dehydropantoate_2-reductase 2-dehydropantoate 2-reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.169 1.1.1.169] Full crystallographic information is available from [http:// | + | 1YON is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=APX:'>APX</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/2-dehydropantoate_2-reductase 2-dehydropantoate 2-reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.169 1.1.1.169] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YON OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Abell, C.]] | [[Category: Abell, C.]] | ||
| - | [[Category: Blundell, T | + | [[Category: Blundell, T L.]] |
[[Category: Ciulli, A.]] | [[Category: Ciulli, A.]] | ||
| - | [[Category: Lobley, C | + | [[Category: Lobley, C M.C.]] |
| - | [[Category: Smith, A | + | [[Category: Smith, A G.]] |
| - | [[Category: Tuck, K | + | [[Category: Tuck, K L.]] |
[[Category: Williams, G.]] | [[Category: Williams, G.]] | ||
[[Category: APX]] | [[Category: APX]] | ||
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[[Category: secondary alcohol dehydrogenase]] | [[Category: secondary alcohol dehydrogenase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:07:32 2008'' |
Revision as of 14:07, 21 February 2008
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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 with as ligand. Active as 2-dehydropantoate 2-reductase, with EC number 1.1.1.169 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 Feb 21 16:07:32 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
