2b0q: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: left|200px<br /><applet load="2b0q" size="450" color="white" frame="true" align="right" spinBox="true" caption="2b0q, resolution 2.700Å" /> '''Crystal Structure O... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2b0q.gif|left|200px]]<br /><applet load="2b0q" size=" | [[Image:2b0q.gif|left|200px]]<br /><applet load="2b0q" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2b0q, resolution 2.700Å" /> | caption="2b0q, resolution 2.700Å" /> | ||
'''Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Neomycin B Complex'''<br /> | '''Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Neomycin B Complex'''<br /> | ||
==Overview== | ==Overview== | ||
The misuse of antibiotics has selected for bacteria that have evolved | 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== | ==About this Structure== | ||
2B0Q is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis] with MG, ADP and NMY as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | 2B0Q is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=ADP:'>ADP</scene> and <scene name='pdbligand=NMY:'>NMY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1L8U. 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B0Q OCA]. | ||
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Kanamycin kinase]] | [[Category: Kanamycin kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Berghuis, A | [[Category: Berghuis, A M.]] | ||
[[Category: Fong, D | [[Category: Fong, D H.]] | ||
[[Category: ADP]] | [[Category: ADP]] | ||
[[Category: MG]] | [[Category: MG]] | ||
| Line 21: | Line 21: | ||
[[Category: protein kinase-like]] | [[Category: protein kinase-like]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:32:56 2008'' | ||
