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Crystal structure of the Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyltransferase L160I mutant: insights into the inhibitor designCrystal structure of the Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyltransferase L160I mutant: insights into the inhibitor design
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a potential target for structure-based inhibitor design for the treatment of parasitic diseases. We created point mutants of Thermoanaerobacter tengcongensis HGPRT and tested their activities to identify side chains that were important for function. Mutating residues Leu160 and Lys133 substantially diminished the activity of HGPRT, confirming their importance in catalysis. All 11 HGPRT mutants were subject to crystallization screening. The crystal structure of one mutant, L160I, was determined at 1.7 A resolution. Surprisingly, the active site is occupied by a peptide from the N-terminus of a neighboring tetramer. These crystal contacts suggest an alternate strategy for structure-based inhibitor design. Crystal structure of Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyl transferase L160I mutant--insights into inhibitor design.,Chen Q, You D, Liang Y, Su X, Gu X, Luo M, Zheng X FEBS J. 2007 Sep;274(17):4408-15. Epub 2007 Jul 27. PMID:17662107[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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