2bkk
From Proteopedia
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| - | [[Image:2bkk.gif|left|200px]]<br /><applet load="2bkk" size=" | + | [[Image:2bkk.gif|left|200px]]<br /><applet load="2bkk" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2bkk, resolution 2.15Å" /> | caption="2bkk, resolution 2.15Å" /> | ||
'''CRYSTAL STRUCTURE OF AMINOGLYCOSIDE PHOSPHOTRANSFERASE APH (3')-IIIA IN COMPLEX WITH THE INHIBITOR AR_3A'''<br /> | '''CRYSTAL STRUCTURE OF AMINOGLYCOSIDE PHOSPHOTRANSFERASE APH (3')-IIIA IN COMPLEX WITH THE INHIBITOR AR_3A'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2BKK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis] with MG and ADP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Kanamycin_kinase Kanamycin kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.95 2.7.1.95] Known structural/functional Site: <scene name='pdbsite=AC1:Mg Binding Site For Chain C'>AC1</scene>. Full crystallographic information is available from [http:// | + | 2BKK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=ADP:'>ADP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Kanamycin_kinase Kanamycin kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.95 2.7.1.95] Known structural/functional Site: <scene name='pdbsite=AC1:Mg+Binding+Site+For+Chain+C'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BKK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:25:09 2008'' |
Revision as of 08:25, 3 February 2008
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CRYSTAL STRUCTURE OF AMINOGLYCOSIDE PHOSPHOTRANSFERASE APH (3')-IIIA IN COMPLEX WITH THE INHIBITOR AR_3A
Overview
Aminoglycoside phosphotransferase (3')-IIIa (APH) is a bacterial kinase, that confers antibiotic resistance to many pathogenic bacteria and shares, structural homology with eukaryotic protein kinases. We report here the, crystal structure of APH, trapped in an inactive conformation by a, tailor-made inhibitory ankyrin repeat (AR) protein, at 2.15 A resolution., The inhibitor was selected from a combinatorial library of designed AR, proteins. The AR protein binds the C-terminal lobe of APH and thereby, stabilizes three alpha helices, which are necessary for substrate binding, in a significantly displaced conformation. BIAcore analysis and kinetic, enzyme inhibition experiments are consistent with the proposed allosteric, inhibition mechanism. In contrast to most small-molecule kinase, inhibitors, the AR proteins are not restricted to active site binding, allowing for higher specificity. Inactive conformations of, pharmaceutically relevant enzymes, as can be elucidated with the approach, presented here, represent powerful starting points for rational drug, design.
About this Structure
2BKK is a Protein complex structure of sequences from Enterococcus faecalis with and as ligands. Active as Kanamycin kinase, with EC number 2.7.1.95 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Allosteric inhibition of aminoglycoside phosphotransferase by a designed ankyrin repeat protein., Kohl A, Amstutz P, Parizek P, Binz HK, Briand C, Capitani G, Forrer P, Pluckthun A, Grutter MG, Structure. 2005 Aug;13(8):1131-41. PMID:16084385
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Categories: Enterococcus faecalis | Kanamycin kinase | Protein complex | Amstutz, P. | Binz, H.K. | Briand, C. | Capitani, G. | Forrer, P. | Grutter, M.G. | Kohl, A. | Parizek, P. | Pluckthun, A. | ADP | MG | Ankyrin repeat | Antibiotic resistance | Atp-binding | Co-crystallization | Designed repeat protein | Drug design | Enzyme inhibition | Inhibitor design | Kinase | Kinase inhibition | Plasmid | Transferase
