2geb
From Proteopedia
(New page: 200px<br /><applet load="2geb" size="350" color="white" frame="true" align="right" spinBox="true" caption="2geb, resolution 1.70Å" /> '''Crystal structure of...) |
|||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a potential | + | 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. |
==About this Structure== | ==About this Structure== | ||
| Line 23: | Line 23: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:30:53 2008'' |
Revision as of 15:30, 21 February 2008
|
Crystal structure of the Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyltransferase L160I mutant: insights into the inhibitor design
Overview
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.
About this Structure
2GEB is a Single protein structure of sequence from Thermoanaerobacter tengcongensis with as ligand. Active as Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 Full crystallographic information is available from OCA.
Reference
Crystal structure of Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyl transferase L160I mutant--insights into inhibitor design., Chen Q, You D, Liang Y, Su X, Gu X, Luo M, Zheng X, FEBS J. 2007 Sep;274(17):4408-15. Epub 2007 Jul 27. PMID:17662107
Page seeded by OCA on Thu Feb 21 17:30:53 2008
