1yfz

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spinqualitylabelsall models 1yfz, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Novel IMP Binding in Feedback Inhibition of Hypoxanthine-Guanine Phosphoribosyltransferase from Thermoanaerobacter tengcongensis

Overview

Crystal structures of Thermoanaerobacter tengcongensis, hypoxanthine-guanine phosphoribosyltransferase (HGPRT) apoenzyme and the, enzyme-inosine monophosphate (IMP) complex have been determined to 2.5A, and 2.2A resolution, respectively. The active form of the enzyme was, identified as a tetramer in solution and the K(i) value of IMP was, measured to be 45 microM for alpha-D-phosphoribosyl-1-pyrophosphate, (PRPP). Conformation of the flexible loop in T.tengcongensis HGPRT, which, is involved in substrate PRPP binding, is different from that observed in, phosphoribosyltransferases (PRTs). It contains a 3-10 helix, and a unique, double serine repeat. This loop is ordered even in the apoenzyme and, assumes a half-closed conformation. The primary magnesium ion is directly, coordinated by side-chains of Glu101 and Asp102, and water molecules in, the apoenzyme, suggesting a possible prerequisite role for substrate PRPP, binding. Most interestingly, an alternative IMP binding mode is found in, the structure of T.tengcongensis HGPRT-IMP complex. The 5'-phosphate of, IMP occupies the PPi position usually seen in PRT-PRPP complexes. This new, observation is consistent with the lower K(i) value of IMP and may suggest, a mechanism involving multiple modes of interactions between IMP and, T.tengcongensis HGPRT in product release and feedback inhibition. The, structure of T.tengcongensis HGPRT is compared with those of mesophilic, HPRTs, and several possible features contributing to its thermostability, are elucidated. Overall, T.tengcongensis HGPRT appears to be more diverged, from other PRTs.

About this Structure

1YFZ is a Single protein structure of sequence from Thermoanaerobacter tengcongensis with ACT, MG and IMP as ligands. Active as Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 Full crystallographic information is available from OCA.

Reference

Alternative IMP binding in feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase from Thermoanaerobacter tengcongensis., Chen Q, Liang Y, Su X, Gu X, Zheng X, Luo M, J Mol Biol. 2005 May 20;348(5):1199-210. Epub 2005 Apr 7. PMID:15854655

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