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PDBsum entry 4gtu

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Transferase PDB id
4gtu
Jmol
Contents
Protein chain
(+ 2 more) 217 a.a. *
* Residue conservation analysis

References listed in PDB file
Key reference
Title An asparagine-Phenylalanine substitution accounts for catalytic differences between hgstm3-3 and other human class mu glutathione s-Transferases.
Authors Y.V.Patskovsky, L.N.Patskovska, I.Listowsky.
Ref. Biochemistry, 1999, 38, 16187-16194. [DOI no: 10.1021/bi991714t]
PubMed id 10587441
Abstract
The hGSTM3 subunit, which is preferentially expressed in germ-line cells, has the greatest sequence divergence among the human mu class glutathione S-transferases. To determine a structural basis for the catalytic differences between hGSTM3-3 and other mu class enzymes, chimeric proteins were designed by modular interchange of the divergent C-terminal domains of hGSTM3 and hGSTM5 subunits. Replacement of 24 residues of the C-terminal segment of either subunit produced chimeric enzymes with catalytic properties that reflected those of the wild-type enzyme from which the C-terminus had been derived. Deletion of the tripeptide C-terminal extension found only in the hGSTM3 subunit had no effect on catalysis. The crystal structure determined for a ligand-free hGSTM3 subunit indicates that an Asn212 residue of the C-terminal domain is near a hydrophobic cluster of side chains formed in part by Ile13, Leu16, Leu114, Ile115, Tyr119, Ile211, and Trp218. Accordingly, a series of point mutations were introduced into the hGSTM3 subunit, and it was indeed determined that a Y119F mutation considerably enhanced the turnover rate of the enzyme for nucleophilic aromatic substitution reactions. A more striking effect was observed for a double mutant (Y119F/N212F) which had a k(cat)/K(m)(CDNB) value of 7.6 x 10(5) s(-)(1) M(-)(1) as compared to 4.9 x 10(3) s(-)(1) M(-)(1) for the wild-type hGSTM3-3 enzyme. The presence of a polar Asn212 in place of a Phe residue found in the cognate position of other mu class glutathione S-transferases, therefore, has a marked influence on catalysis by hGSTM3-3.
Secondary reference #1
Title Isolation and analysis of the gene and cdna for a human mu class glutathione s-Transferase, Gstm4.
Authors K.E.Comstock, K.J.Johnson, D.Rifenbery, W.D.Henner.
Ref. J Biol Chem, 1993, 268, 16958-16965.
PubMed id 8349586
Abstract
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