1l8t
From Proteopedia
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|PDB= 1l8t |SIZE=350|CAPTION= <scene name='initialview01'>1l8t</scene>, resolution 2.4Å | |PDB= 1l8t |SIZE=350|CAPTION= <scene name='initialview01'>1l8t</scene>, resolution 2.4Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=KAN:KANAMYCIN+A'>KAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1j7i|1J7I]], [[1j7l|1J7L]], [[1j7u|1J7U]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1l8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8t OCA], [http://www.ebi.ac.uk/pdbsum/1l8t PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1l8t RCSB]</span> | ||
}} | }} | ||
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[[Category: Berghuis, A M.]] | [[Category: Berghuis, A M.]] | ||
[[Category: Fong, D H.]] | [[Category: Fong, D H.]] | ||
| - | [[Category: ADP]] | ||
| - | [[Category: KAN]] | ||
| - | [[Category: MG]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:59:40 2008'' |
Revision as of 18:59, 30 March 2008
| |||||||
| , resolution 2.4Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | Kanamycin kinase, with EC number 2.7.1.95 | ||||||
| Related: | 1J7I, 1J7L, 1J7U
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Kanamycin A Complex
Overview
The misuse of antibiotics has selected for bacteria that have evolved mechanisms for evading the effects of these drugs. For aminoglycosides, a group of clinically important bactericidal antibiotics that target the A-site of the 16S ribosomal RNA, the most common mode of resistance is enzyme-catalyzed chemical modification of the drug. While aminoglycosides are structurally diverse, a single enzyme can confer resistance to many of these antibiotics. For example, the aminoglycoside kinase APH(3')-IIIa, produced by pathogenic Gram-positive bacteria such as enterococci and staphylococci, is capable of detoxifying at least 10 distinct aminoglycosides. Here we describe the crystal structures of APH(3')-IIIa in complex with ADP and kanamycin A or neomycin B. These structures reveal that the basis for this enzyme's substrate promiscuity is the presence of two alternative subsites in the antibiotic binding pocket. Furthermore, comparison between the A-site of the bacterial ribosome and APH(3')-IIIa shows that mimicry is the second major factor in dictating the substrate spectrum of APH(3')-IIIa. These results suggest a potential strategy for drug design aimed at circumventing antibiotic resistance.
About this Structure
1L8T is a Single protein structure of sequence from Enterococcus faecalis. Full crystallographic information is available from OCA.
Reference
Substrate promiscuity of an aminoglycoside antibiotic resistance enzyme via target mimicry., Fong DH, Berghuis AM, EMBO J. 2002 May 15;21(10):2323-31. PMID:12006485
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