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Crystal structure of homoisocitrate dehydrogenase from Schizosaccharomyces pombe.

ABSTRACT: Homoisocitrate dehydrogenase (HICDH) catalyzes the conversion of homoisocitrate to 2-oxoadipate, the third enzymatic step in the ?-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 ?-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.

SUBMITTER: Bulfer SL

PROVIDER: S-EPMC4332711 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Crystal structure of homoisocitrate dehydrogenase from Schizosaccharomyces pombe.

Bulfer Stacie L SL Hendershot Jenna M JM Trievel Raymond C RC

Proteins 20111122 2

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 othe ...[more]

PMID: 22105743

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