Disease relevance of C05662

• Substrate specificity of two homoisocitrate dehydrogenases derived from Deinococcus radiodurans and Saccharomyces cerevisiae was analyzed using a series of synthetic substrate analogs, which indicated a relatively broad substrate specificity of these enzymes [1].
• We do not observe HACN-catalysed 'homocitrate dehydratase' activity; however, we have observed that ACN can catalyse the dehydration of (R)-homocitrate to cis-homoaconitate, but HACN is required for subsequent conversion of cis-homoaconitate into homoisocitrate [2].
• This suggests that the in vivo process for conversion of homocitrate into homoisocitrate requires two enzymes, in simile with the propionate utilization pathway from Escherichia coli [2].

High impact information on C05662

• It is of interest that HICDH catalyzes the reaction with isocitrate about 20 times more efficiently than the reaction with the putative native substrate, homoisocitrate [3].
• The values of apparent S0.5 for total isocitrate and total garcinia acid are similar with both enzymes; the apparent S0.5 of total homoisocitrate is two- to threefold higher than that of total isocitrate with the DPN-linked enzyme [4].
• Beta-decarboxylating dehydrogenases comprise 3-isopropylmalate dehydrogenase, isocitrate dehydrogenase, and homoisocitrate dehydrogenase [5].
• Saturation mutagenesis of Dra-HICDH Arg87 was next performed because an orthologous Arg85 to valine mutation in Tth-HICDH results in loss of activity toward isocitrate, but in retention of activity toward homoisocitrate [6].
• Substrate specificity analysis and inhibitor design of homoisocitrate dehydrogenase [1].

References