1FW1

Glutathione transferase zeta/maleylacetoacetate isomerase

Summary for 1FW1

• Entry DOI: 10.2210/pdb1fw1/pdb
• Descriptor: GLUTATHIONE TRANSFERASE ZETA, SULFATE ION, 2,3-DIHYDROXY-1,4-DITHIOBUTANE, ... (5 entities in total)
• Functional Keywords: glutathione transferase, isomerase-transferase complex, isomerase/transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): O43708
• Total number of polymer chains: 1
• Total formula weight: 24665.62

Authors

Polekhina, G.,Board, P.G.,Blackburn, A.C.,Parker, M.W. (deposition date: 2000-09-20, release date: 2001-09-26, Last modification date: 2011-07-13)

Primary citation

Polekhina, G.,Board, P.G.,Blackburn, A.C.,Parker, M.W.
Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity.
Biochemistry, 40:1567-1576, 2001

PubMed Abstract: Maleylacetoacetate isomerase (MAAI), a key enzyme in the metabolic degradation of phenylalanine and tyrosine, catalyzes the glutathione-dependent isomerization of maleylacetoacetate to fumarylacetoacetate. Deficiencies in enzymes along the degradation pathway lead to serious diseases including phenylketonuria, alkaptonuria, and the fatal disease, hereditary tyrosinemia type I. The structure of MAAI might prove useful in the design of inhibitors that could be used in the clinical management of the latter disease. Here we report the crystal structure of human MAAI at 1.9 A resolution in complex with glutathione and a sulfate ion which mimics substrate binding. The enzyme has previously been shown to belong to the zeta class of the glutathione S-transferase (GST) superfamily based on limited sequence similarity. The structure of MAAI shows that it does adopt the GST canonical fold but with a number of functionally important differences. The structure provides insights into the molecular bases of the remarkable array of different reactions the enzyme is capable of performing including isomerization, oxygenation, dehalogenation, peroxidation, and transferase activity.

PubMed: 11327815
DOI: 10.1021/bi002249z

Experimental method

X-RAY DIFFRACTION (1.9 Å)