Page 6 - U. Protein structure and function

[U. Protein structure and function-3]

Malate Dehydrogenase a novel ppGpp binding protein

Rana Aqeel Afzal¹, Che-Hun Jung¹

¹Molecular Medicine, Chonnam National University, Gwangju 61186, Korea

The citric acid cycle is the central oxidative pathway in prokaryotes and eukaryotes under aerobic conditions. One
of the reactions in the cycle is the conversion of malate to oxaloacetate, catalyzed by NAD+- or NADP+-dependent
malate dehydrogenase (MDH). Although MDH has been described as an enzyme for the oxidative TCA cycle, the

reaction that forms oxaloacetate is highly unfavorable thermodynamically. For this reason, it has been suggested

that this enzyme has other functions inside the cell. MDH from Escherichia coli under anaerobic conditions
participates in a reductive TCA cycle (converting oxaloacetate to malate) that produces succinic acid. The alarmone
ppGpp is involved in growth regulation and various stress responses in bacteria. It induces profound transcriptional

alterations, including the repression of stable RNA synthesis and induction of stress response factors and genes
required for amino acid biosynthesis and transport. In this study, we report MDH as a novel ppGpp-binding protein

with a high affinity. No activity change associated with the ppGpp-binding suggests that ppGpp does not bind at
active site of MDH. Further experiments for ppGpp-binding site on MDH, and its unidentified functions in E.coli

are in process.