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Publication Abstract from PubMed

The mutant E270A of Thermus thermophilus 3-isopropylmalate dehydrogenase exhibits largely reduced ( approximately 1%) catalytic activity and negligible activation by K(+) compared to the wild-type enzyme. A 3-4kcal/mol increase in the activation energy of the catalysed reaction upon this mutation could also be predicted by QM/MM calculations. In the X-ray structure of the E270A mutant a water molecule was observed to take the place of K(+). SAXS and FRET experiments revealed the essential role of E270 in stabilisation of the active domain-closed conformation of the enzyme. In addition, E270 seems to position K(+) into close proximity of the nicotinamide ring of NAD(+) and the electron-withdrawing effect of K(+) may help to polarise the aromatic ring in order to aid the hydride-transfer.

Glutamate 270 plays an essential role in K(+)-activation and domain closure of Thermus thermophilus isopropylmalate dehydrogenase.,Graczer E, Pallo A, Olah J, Szimler T, Konarev PV, Svergun DI, Merli A, Zavodszky P, Weiss MS, Vas M FEBS Lett. 2015 Jan 16;589(2):240-5. doi: 10.1016/j.febslet.2014.12.005. Epub, 2014 Dec 10. PMID:25497013^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.