1nd4: Difference between revisions

==Overview==

A major factor in the emergence of antibiotic resistance is the existence, of enzymes that chemically modify common antibiotics. The genes for these, enzymes are commonly carried on mobile genetic elements, facilitating, their spread. One such class of enzymes is the aminoglycoside, phosphotransferase (APH) family, which uses ATP-mediated phosphate, transfer to chemically modify and inactivate aminoglycoside antibiotics, such as streptomycin and kanamycin. As part of a program to define the, molecular basis for aminoglycoside recognition and inactivation by such, enzymes, we have determined the high resolution (2.1A) crystal structure, of aminoglycoside-3'-phosphotransferase-IIa (APH(3')-IIa) in complex with, kanamycin. The structure was solved by molecular replacement using, multiple models derived from the related, aminoglycoside-3'-phosphotransferase-III enzyme (APH(3')-III), and refined, to an R factor of 0.206 (R(free) 0.238). The bound kanamycin molecule is, very well defined and occupies a highly negatively charged cleft formed by, the C-terminal domain of the enzyme. Adjacent to this is the binding site, for ATP, which can be modeled on the basis of nucleotide complexes of, APH(3')-III; only one change is apparent with a loop, residues 28-34, in a, position where it could fold over an incoming nucleotide. The three rings, of the kanamycin occupy distinct sub-pockets in which a highly acidic, loop, residues 151-166, and the C-terminal residues 260-264 play important, parts in recognition. The A ring, the site of phosphoryl transfer, is, adjacent to the catalytic base Asp190. These results give new information, on the basis of aminoglycoside recognition, and on the relationship, between this phosphotransferase family and the protein kinases.

==About this Structure==

1ND4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae] with MG, ACT, NA and KAN 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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ND4 OCA].

 

The crystal structure of aminoglycoside-3'-phosphotransferase-IIa, an enzyme responsible for antibiotic resistance., Nurizzo D, Shewry SC, Perlin MH, Brown SA, Dholakia JN, Fuchs RL, Deva T, Baker EN, Smith CA, J Mol Biol. 2003 Mar 21;327(2):491-506. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12628253 12628253]

[[Category: Single protein]]

[[Category: Baker, E.N.]]

[[Category: Nurizzo, D.]]

[[Category: Shewry, S.C.]]

[[Category: Smith, C.A.]]