1fw1
GLUTATHIONE TRANSFERASE ZETA/MALEYLACETOACETATE ISOMERASE
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OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Tyrosinemia, type Ib OMIM:[603758]
About this StructureAbout this Structure
1FW1 is a Single protein structure of sequence from Homo sapiens with SO4, DTT and GSH as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity., Polekhina G, Board PG, Blackburn AC, Parker MW, Biochemistry. 2001 Feb 13;40(6):1567-76. PMID:11327815
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