Crystal structure of homoisocitrate dehydrogenase from Schizosaccharomyces pombe

• Published in: Proteins, structure, function, and bioinformatics Vol. 80; no. 2; pp. 661 - 666
• Main Authors: Bulfer, Stacie L., Hendershot, Jenna M., Trievel, Raymond C.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-02-2012; Wiley Subscription Services, Inc
• Subjects: 60 APPLIED LIFE SCIENCES; ADDITIVES; Alcohol Oxidoreductases - chemistry; Alcohol Oxidoreductases - metabolism; amino acid metabolism; AMINO ACIDS; ASPERGILLUS; BASIC BIOLOGICAL SCIENCES; BIOSYNTHESIS; CANDIDA; Catalytic Domain; CITRIC ACID; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; Crystallography, X-Ray; DECARBOXYLASES; DECARBOXYLATION; ENZYMES; EUGLENA; FUNGI; LEUCINE; LYSINE; lysine biosynthesis; METABOLISM; Models, Molecular; NAD; OXIDOREDUCTASES; Protein Conformation; Schizosaccharomyces pombe Proteins - chemistry; Schizosaccharomyces pombe Proteins - metabolism; Structural Homology, Protein; SUBSTRATES; TARTRATES; X-ray crystallography; β-hydroxyacid oxidative decarboxylase; X-ray crystallography; lysine biosynthesis; β-hydroxyacid oxidative decarboxylase; amino acid metabolism
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.23231

Homoisocitrate dehydrogenase (HICDH) catalyzes the conversion of homoisocitrate to 2-oxoadipate, the third enzymatic step in the α-aminoadipate pathway by which lysine is synthesized in fungi and certain archaebacteria. This enzyme represents a potential target for anti-fungal drug design. Here, we describe the first crystal structures of a fungal HICDH, including structures of an apoenzyme and a binary complex with a glycine tri-peptide. The structures illustrate the homology of HICDH with other β-hydroxyacid oxidative decarboxylases and reveal key differences with the active site of Thermus thermophilus HICDH that provide insights into the differences in substrate specificity of these enzymes.