2ov8
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(New page: 200px<br /><applet load="2ov8" size="350" color="white" frame="true" align="right" spinBox="true" caption="2ov8, resolution 2.580Å" /> '''Crystal Structure o...)
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Revision as of 13:04, 23 January 2008
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Crystal Structure of StaL
Overview
Over the past decade, antimicrobial resistance has emerged as a major, public health crisis. Glycopeptide antibiotics such as vancomycin and, teicoplanin are clinically important for the treatment of Gram-positive, bacterial infections. StaL is a 3'-phosphoadenosine, 5'-phosphosulfate-dependent sulfotransferase capable of sulfating the, cross-linked heptapeptide substrate both in vivo and in vitro, yielding, the product A47934, a unique teicoplanin-class glycopeptide antibiotic., The sulfonation reaction catalyzed by StaL constitutes the final step in, A47934 biosynthesis. Here we report the crystal structure of StaL and its, complex with the cofactor product 3'-phosphoadenosine 5'-phosphate. This, is only the second prokaryotic sulfotransferase to be structurally, characterized. StaL belongs to the large sulfotransferase family and shows, higher similarity to cytosolic sulfotransferases (ST) than to the, bacterial ST (Stf0). StaL has a novel dimerization motif, different from, any other STs that have been structurally characterized. We have also, applied molecular modeling to investigate the binding mode of the unique, substrate, desulfo-A47934. Based on the structural analysis and modeling, results, a series of residues was mutated and kinetically characterized., In addition to the conserved residues (Lys(12), His(67), and Ser(98)), molecular modeling, fluorescence quenching experiments, and mutagenesis, studies identified several other residues essential for substrate binding, and/or activity, including Trp(34), His(43), Phe(77), Trp(132), and, Glu(205).
About this Structure
2OV8 is a Single protein structure of sequence from Streptomyces toyocaensis. Full crystallographic information is available from OCA.
Reference
Crystal structure of StaL, a glycopeptide antibiotic sulfotransferase from Streptomyces toyocaensis., Shi R, Lamb SS, Bhat S, Sulea T, Wright GD, Matte A, Cygler M, J Biol Chem. 2007 Apr 27;282(17):13073-86. Epub 2007 Feb 28. PMID:17329243
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