First time at Proteopedia? Click on the green links: they change the 3D image. Click and drag the molecules. Proteopedia is a 3D, interactive encyclopedia of proteins, RNA, DNA and other molecules. With a free user account, you can edit pages in Proteopedia. Visit the Main Page to learn more.
4gtu
From Proteopedia
| 4gtu, resolution 3.30Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Gene: | GSTM4 (Homo sapiens) | ||||||||
| Activity: | Glutathione transferase, with EC number 2.5.1.18 | ||||||||
| Related: | 1gtu, 2gtu, 3gtu | ||||||||
| |||||||||
| |||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
LIGAND-FREE HOMODIMERIC HUMAN GLUTATHIONE S-TRANSFERASE M4-4
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.
An asparagine-phenylalanine substitution accounts for catalytic differences between hGSTM3-3 and other human class mu glutathione S-transferases., Patskovsky YV, Patskovska LN, Listowsky I, Biochemistry. 1999 Dec 7;38(49):16187-94. PMID:10587441
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
4gtu is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Patskovsky YV, Patskovska LN, Listowsky I. An asparagine-phenylalanine substitution accounts for catalytic differences between hGSTM3-3 and other human class mu glutathione S-transferases. Biochemistry. 1999 Dec 7;38(49):16187-94. PMID:10587441
