Studying the signaling role of 2-oxoglutaric acid using analogs that mimic the ketone and ketal forms of 2-oxoglutaric acid.
2-Oxoglutaric acid (2-OG), a Krebs cycle intermediate, is a signaling molecule in many organisms. To determine which form of 2-OG, the ketone or the ketal form, is responsible for its signaling function, we have synthesized and characterized various 2-OG analogs. Only 2-methylenepentanedioic acid (2-MPA), which resembles closely the ketone form of 2-OG, is able to elicit cell responses in the cyanobacterium Anabaena by inducing nitrogen-fixing cells called heterocysts. None of the analogs mimicking the ketal form of 2-OG are able to induce heterocysts because none of them are able to interact with NtcA, a 2-OG sensor. NtcA interacts with 2-MPA and 2-OG in a similar manner, and it is necessary for heterocyst differentiation induced by 2-MPA. Therefore, it is primarily the ketone form that is responsible for the signaling role of 2-OG in Anabaena.
Chen
Han
H
College of Chemistry and Molecular Sciences, Wuhan University, 430072 Wuhan, China.
Laurent
Sophie
S
Bédu
Sylvie
S
Ziarelli
Fabio
F
Chen
Hai-Li
HL
Cheng
Yong
Y
Zhang
Cheng-Cai
CC
Peng
Ling
L
D017033:Anabaena / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D018360:Crystallography, X-Ray; D003998:Dicarboxylic Acids / Q000737:chemistry*; D007656:Ketoglutaric Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007659:Ketones / Q000737:chemistry*; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
C514880:2-methylenepentanedioic acid; D003998:Dicarboxylic Acids; D007656:Ketoglutaric Acids; D007659:Ketones