PMID:17662107

Citation	Chen, Q, You, D, Liang, Y, Su, X, Gu, X, Luo, M and Zheng, X (2007) Crystal structure of Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyl transferase L160I mutant--insights into inhibitor design. FEBS J. 274:4408-15
Abstract	Hypoxanthine-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.
Links	PubMed Online version:10.1111/j.1742-4658.2007.05970.x
Keywords	Crystallography, X-Ray; Enzyme Inhibitors/chemistry; Enzyme Inhibitors/pharmacology; Hypoxanthine Phosphoribosyltransferase/antagonists & inhibitors; Hypoxanthine Phosphoribosyltransferase/chemistry; Hypoxanthine Phosphoribosyltransferase/isolation & purification; Models, Molecular; Protein Conformation; Thermoanaerobacter/enzymology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:HPRT		GO:0000100: S-methylmethionine transmembrane transporter activity	ECO:0000250:	UniProtKB:Q8R7L0	F		The main protein ribose-phosphate pyrophosphokinase from the Hakuna Genome, shares a homology with guanine phosphoribosyltransferase with an e score of 4e-10 according to HHPRED. The function and structure of this protein is to design compounds that would be effective inhibitors. "Almost all of the inhibitors available are analogues of the substrate or transition-state. The main drawback of these compounds is that there is poor differential inhibition among various HGPRTs. The reason maybe due to high structure similarity of HGPRTs from different species (especially the active site) even though there is only moderate sequence homology. The key residues in the active site are highly similar among HGPRTs (Table 1)."	complete CACAO 11622
CALS4:Q8R7L0		GO:0000100: S-methylmethionine transmembrane transporter activity	ECO:0000250:	UniProtKB:	F		The function and structure of this protein is to design compounds that would be effective inhibitors. "Almost all of the inhibitors available are analogues of the substrate or transition-state. The main drawback of these compounds is that there is poor differential inhibition among various HGPRTs. The reason maybe due to high structure similarity of HGPRTs from different species (especially the active site) even though there is only moderate sequence homology. The key residues in the active site are highly similar among HGPRTs (Table 1)."	complete CACAO 12083

References

See Help:References for how to manage references in GONUTS.