1l8t

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{{Seed}}
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{{STRUCTURE_1l8t| PDB=1l8t | SCENE= }}
{{STRUCTURE_1l8t| PDB=1l8t | SCENE= }}
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'''Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Kanamycin A Complex'''
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===Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Kanamycin A Complex===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12006485 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12006485}}
==About this Structure==
==About this Structure==
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[[Category: Fong, D H.]]
[[Category: Fong, D H.]]
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:40:35 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 11:58:26 2008''

Revision as of 08:58, 2 July 2008

Image:1l8t.png

Template:STRUCTURE 1l8t

Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Kanamycin A Complex

Template:ABSTRACT PUBMED 12006485

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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