Alternative IMP binding in feedback inhibition of hypoxanthine-guanine   phosphoribosyltransferase from Thermoanaerobacter tengcongensis

doi:10.1016/j.jmb.2005.02.064

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	Alternative IMP binding in feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase from Thermoanaerobacter tengcongensis
	Chen, Q ; Liang, YH ; Su, XD ; Gu, XC ; Zheng, XF ; Luo, M
刊名	分子生物学杂志
	2005
关键词	crystal structure IMP HGPRT feedback inhibition thermostability STATE ANALOG INHIBITOR 2.0 ANGSTROM STRUCTURE CRYSTAL-STRUCTURE XANTHINE PHOSPHORIBOSYLTRANSFERASE ESCHERICHIA-COLI TRANSITION-STATE TRITRICHOMONAS-FETUS PROTEIN STRUCTURES PURINE NUCLEOTIDE TERNARY COMPLEX
DOI	10.1016/j.jmb.2005.02.064
英文摘要	Crystal structures of Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyltransferase (HGPRT) apoenzyme and the enzyme-inosine monophosphate (IMP) complex have been determined to 2.5 &ANGS; and 2.2 &ANGS; 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 pM for α-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; 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. tengcongmsis HGPRT is compared with those of mesophilic HPRTs, and several possible features contributing to its thermostability are elucidated. Overall, T. tengcongmsis HGPRT appears to be more diverged from other PRTs. © 2005 Elsevier Ltd. All rights reserved.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000229054400013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Biochemistry & Molecular Biology; SCI(E); PubMed; 12; ARTICLE; 5; 1199-1210; 348
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/199771]
专题	生命科学学院
推荐引用方式 GB/T 7714	Chen, Q,Liang, YH,Su, XD,et al. Alternative IMP binding in feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase from Thermoanaerobacter tengcongensis[J]. 分子生物学杂志,2005.
APA	Chen, Q,Liang, YH,Su, XD,Gu, XC,Zheng, XF,&Luo, M.(2005).Alternative IMP binding in feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase from Thermoanaerobacter tengcongensis.分子生物学杂志.
MLA	Chen, Q,et al."Alternative IMP binding in feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase from Thermoanaerobacter tengcongensis".分子生物学杂志 (2005).