2GDR

Crystal structure of a bacterial glutathione transferase

Summary for 2GDR

• Entry DOI: 10.2210/pdb2gdr/pdb
• Related: 1F2E 1N2A 1PMT 2GDH
• Descriptor: glutathione S-transferase, GLUTATHIONE (3 entities in total)
• Functional Keywords: protein homodimer, each monomer contains two domains, n-term domain is mixed beta sheets and alpha helices, c-term domain is alpha helical, transferase
• Biological source: Burkholderia xenovorans
• Total number of polymer chains: 6
• Total formula weight: 136374.57

Authors

Tocheva, E.I.,Fortin, P.D.,Eltis, L.D.,Murphy, M.E.P. (deposition date: 2006-03-16, release date: 2006-08-22, Last modification date: 2023-08-30)

Primary citation

Tocheva, E.I.,Fortin, P.D.,Eltis, L.D.,Murphy, M.E.
Structures of Ternary Complexes of BphK, a Bacterial Glutathione S-Transferase That Reductively Dechlorinates Polychlorinated Biphenyl Metabolites.
J.Biol.Chem., 281:30933-30940, 2006

PubMed Abstract: Prokaryotic glutathione S-transferases are as diverse as their eukaryotic counterparts but are much less well characterized. BphK from Burkholderia xenovorans LB400 consumes two GSH molecules to reductively dehalogenate chlorinated 2-hydroxy-6-oxo-6-phenyl-2,4-dienoates (HOPDAs), inhibitory polychlorinated biphenyl metabolites. Crystallographic structures of two ternary complexes of BphK were solved to a resolution of 2.1A. In the BphK-GSH-HOPDA complex, GSH and HOPDA molecules occupy the G- and H-subsites, respectively. The thiol nucleophile of the GSH molecule is positioned for SN2 attack at carbon 3 of the bound HOPDA. The respective sulfur atoms of conserved Cys-10 and the bound GSH are within 3.0A, consistent with product release and the formation of a mixed disulfide intermediate. In the BphK-(GSH)2 complex, a GSH molecule occupies each of the two subsites. The three sulfur atoms of the two GSH molecules and Cys-10 are aligned suitably for a disulfide exchange reaction that would regenerate the resting enzyme and yield disulfide-linked GSH molecules. A second conserved residue, His-106, is adjacent to the thiols of Cys-10 and the GSH bound to the G-subsite and thus may stabilize a transition state in the disulfide exchange reaction. Overall, the structures support and elaborate a proposed dehalogenation mechanism for BphK and provide insight into the plasticity of the H-subsite.

PubMed: 16920719
DOI: 10.1074/jbc.M603125200

Experimental method

X-RAY DIFFRACTION (2.1 Å)