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A conserved dimer and global conformational changes in the structure of apo-PknE Ser/Thr protein kinase from Mycobacterium tuberculosis.

Gay LM, Ng HL, Alber T
J Mol Biol 360 409-20 (2006)
Cited: 45 times
EuropePMC logo PMID: 16762364

Abstract

The "eukaryotic-like" receptor Ser/Thr protein kinases (STPKs) are candidates for the sensors that mediate environmental adaptations of Mycobacterium tuberculosis (Mtb). To define the mechanisms of regulation and substrate recognition, we determined the crystal structure of the ligand-free, activated kinase domain (KD) of the Mtb STPK, PknE. Remarkably, the PknE KD formed a dimer similar to that first observed in the structure of the ATPgammaS complex of the Mtb paralog, PknB. This structural similarity, which occurs despite little sequence conservation between the PknB and PknE dimer interfaces, supports the idea that dimerization regulates the Mtb receptor STPKs. Insertion of the DFG motif into the ATP-binding site and other conformational differences compared the ATPgammaS:PknB complex suggest that apo-PknE is not pre-organized to bind nucleotides. This structure may represent an inactive conformation stabilized by dimerization or, alternatively, an active conformation that reveals shifts that mediate nucleotide exchange and order substrate binding.

Reviews - 2h34 mentioned but not cited (3)

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Articles - 2h34 mentioned but not cited (8)

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  17. Structural Insight into the Activation of PknI Kinase from M. tuberculosis via Dimerization of the Extracellular Sensor Domain. Yan Q, Jiang D, Qian L, Zhang Q, Zhang W, Zhou W, Mi K, Guddat L, Yang H, Rao Z. Structure 25 1286-1294.e4 (2017)
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