PDBsum entry 1mtc

Transferase

PDB id: 1mtc

Contents

Protein chains

217 a.a. *

Ligands

GPR ×2

Waters ×185

* Residue conservation analysis

PDB id:

1mtc

Name:

Transferase

Title:

Glutathione transferase mutant y115f

Structure:

Glutathione s-transferase yb1. Chain: a, b. Synonym: chain 3. Gst m1-1. Gst class-mu 1. Glutathione s-transferase yb-1 subunit. Engineered: yes. Mutation: yes. Other_details: complex with (9r,10r)-9-(s-glutathionyl)-10-hydroxy-9, 10-dihrophenanthrene

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: liver. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.20Å R-factor: 0.203

Authors:

J.E.Ladner,G.Xiao,R.N.Armstrong,G.L.Gilliland

Key ref:

S.G.Codreanu et al. (2002). Local protein dynamics and catalysis: detection of segmental motion associated with rate-limiting product release by a glutathione transferase. Biochemistry, 41, 15161-15172. PubMed id: 12484753 DOI: 10.1021/bi026776p

Date:

20-Sep-02 Release date: 25-Mar-03

Protein chains

P04905  (GSTM1_RAT) -  Glutathione S-transferase Mu 1 from Rattus norvegicus

Seq: 218 a.a.

Struc: 217 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.5.1.18 - glutathione transferase.
• Reaction: RX + glutathione = an S-substituted glutathione + a halide anion + H⁺

RX (Bound ligand (Het Group name = GPR) matches with 57.14% similarity) + glutathione = S-substituted glutathione + halide anion + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1021/bi026776p

Biochemistry 41:15161-15172 (2002)

PubMed id: 12484753

Local protein dynamics and catalysis: detection of segmental motion associated with rate-limiting product release by a glutathione transferase.

S.G.Codreanu, J.E.Ladner, G.Xiao, N.V.Stourman, D.L.Hachey, G.L.Gilliland, R.N.Armstrong.

ABSTRACT

Glutathione transferase rGSTM1-1 catalyzes the addition of glutathione (GSH) to 1-chloro-2,4-dinitrobenzene, a reaction in which the chemical step is 60-fold faster than the physical step of product release. The hydroxyl group of Y115, located in the active site access channel, controls the egress of product from the active site. The Y115F mutant enzyme has a k(cat) (72 s(-)(1)) that is 3.6-fold larger than that of the native enzyme (20 s(-)(1)). Crystallographic observations and evidence from amide proton exchange kinetics are consistent with localized increases in the degree of segmental motion of the Y115F mutant that are coupled to the enhanced rate of product release. The loss of hydrogen bonding interactions involving the hydroxyl group of Y115 is reflected in subtle alterations in the backbone position, an increase in B-factors for structural elements that comprise the channel to the active site, and, most dramatically, a loss of well-defined electron density near the site of mutation. The kinetics of amide proton exchange are also enhanced by a factor between 3 and 12 in these regions, providing direct, quantitative evidence for changes in local protein dynamics affecting product release. The enhanced product release rate is proposed to derive from a small shift in the equilibrium population of protein conformers that permit egress of the product from the active site.