1YFZ

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

1YFZ の概要

• エントリーDOI: 10.2210/pdb1yfz/pdb
• 関連するPDBエントリー: 1R3U
• 分子名称: Hypoxanthine-guanine phosphoribosyltransferase, ACETATE ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: protein-nucleotide complex, transferase
• 由来する生物種: Thermoanaerobacter tengcongensis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46436.92

構造登録者

Chen, Q.,Liang, Y.,Su, X.,Gu, X.,Zheng, X.,Luo, M. (登録日: 2005-01-04, 公開日: 2005-05-10, 最終更新日: 2023-08-23)

主引用文献

Chen, Q.,Liang, Y.,Su, X.,Gu, X.,Zheng, X.,Luo, M.
Alternative IMP Binding in Feedback Inhibition of Hypoxanthine-Guanine Phosphoribosyltransferase from Thermoanaerobacter tengcongensis.
J.Mol.Biol., 348:1199-1210, 2005

PubMed Abstract: 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.

PubMed: 15854655
DOI: 10.1016/j.jmb.2005.02.064

実験手法

X-RAY DIFFRACTION (2.2 Å)