2GEB

Crystal structure of the Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyltransferase L160I mutant: insights into the inhibitor design

Summary for 2GEB

• Entry DOI: 10.2210/pdb2geb/pdb
• Related: 1R3U 1YFZ
• Descriptor: Hypoxanthine-guanine phosphoribosyltransferase, CALCIUM ION (3 entities in total)
• Functional Keywords: hgprt, mutant, inhibitor design, selectivity, transferase
• Biological source: Thermoanaerobacter tengcongensis
• Total number of polymer chains: 1
• Total formula weight: 20849.40

Authors

Chen, Q.,Luo, M. (deposition date: 2006-03-19, release date: 2007-04-03, Last modification date: 2024-02-14)

Primary citation

Chen, Q.,You, D.,Liang, Y.,Su, X.,Gu, X.,Luo, M.,Zheng, X.
Crystal structure of Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyl transferase L160I mutant--insights into inhibitor design.
Febs J., 274:4408-4415, 2007

PubMed 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.

PubMed: 17662107
DOI: 10.1111/j.1742-4658.2007.05970.x

Experimental method

X-RAY DIFFRACTION (1.7 Å)