This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
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...) |
|||
| Line 1: | Line 1: | ||
| - | [[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== | ||
| Line 15: | Line 15: | ||
[[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]] | ||
| Line 28: | Line 28: | ||
[[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
|
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
