1gti
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(New page: 200px<br /><applet load="1gti" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gti, resolution 3.0Å" /> '''MODIFIED GLUTATHIONE ...)
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Revision as of 14:09, 20 November 2007
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MODIFIED GLUTATHIONE S-TRANSFERASE (PI) COMPLEXED WITH S (P-NITROBENZYL)GLUTATHIONE
Overview
The three-dimensional structure of mouse liver glutathione S-transferase, P1-1 carboxymethylated at Cys-47 and its complex with, S-(p-nitrobenzyl)glutathione have been determined by x-ray diffraction, analysis. The structure of the modified enzyme described here is the first, structural report for a Pi class glutathione S-transferase with no, glutathione, glutathione S-conjugate, or inhibitor bound. It shows that, part of the active site area, which includes helix alphaB and helix 310B, is disordered. However, the environment of Tyr-7, an essential residue for, the catalytic reaction, remains unchanged. The position of the sulfur atom, of glutathione is occupied in the ligand-free enzyme by a water molecule, that is at H-bond distance from Tyr-7. We do not find any structural, evidence for a tyrosinate form, and therefore our results suggest that, Tyr-7 is not acting as a general base abstracting the proton from the, thiol group of glutathione. The binding of the inhibitor, S-(p-nitrobenzyl)-glutathione to the carboxymethylated enzyme results in a, partial restructuring of the disordered area. The modification of Cys-47, sterically hinders structural organization of this region, and although it, does not prevent glutathione binding, it significantly reduces the, affinity. A detailed kinetic study of the modified enzyme indicates that, the carboxymethylation increases the Km for glutathione by 3 orders of, magnitude, although the enzyme can function efficiently under saturating, conditions.
About this Structure
1GTI is a Single protein structure of sequence from Mus musculus with GTB as ligand. Active as Glutathione transferase, with EC number 2.5.1.18 Full crystallographic information is available from OCA.
Reference
The three-dimensional structure of Cys-47-modified mouse liver glutathione S-transferase P1-1. Carboxymethylation dramatically decreases the affinity for glutathione and is associated with a loss of electron density in the alphaB-310B region., Vega MC, Walsh SB, Mantle TJ, Coll M, J Biol Chem. 1998 Jan 30;273(5):2844-50. PMID:9446594
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