Allosteric activation mechanism of the Mycobacterium tuberculosis receptor Ser/Thr protein kinase, PknB.
Allosteric activation mechanism of the Mycobacterium tuberculosis receptor Ser/Thr protein kinase, PknB.
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DOI：
10.1016/j.str.2010.09.019
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发表时间：
2010-12-08
期刊：
影响因子：
5.7
通讯作者：
Alber, Tom
中科院分区：
文献类型：
--
作者：
Lombana, T. Noelle;Echols, Nathaniel;Good, Matthew C.;Thomsen, Nathan D.;Ng, Ho-Leung;Greenstein, Andrew E.;Falick, Arnold M.;King, David S.;Alber, Tom
The essential Mycobacterium tuberculosis Ser/Thr protein kinase (STPK), PknB, plays a key role in regulating growth and division, but the structural basis of activation has not been defined. Here we provide biochemical and structural evidence that dimerization through the kinase-domain (KD) N-lobe activates PknB by an allosteric mechanism. Promoting KD pairing using a small-molecule dimerizer stimulates the unphosphorylated kinase, and substitutions that disrupt N-lobe pairing decrease phosphorylation activity in vitro and in vivo. Multiple crystal structures of two monomeric PknB KD mutants in complex with nucleotide reveal diverse inactive conformations that contain large active-site distortions that propagate >30 Å from the mutation site. These results define flexible, inactive structures of a monomeric bacterial receptor KD and show how “back-to-back” N-lobe dimerization stabilizes the active KD conformation. This general mechanism of bacterial receptor STPK activation affords insights into the regulation of homologous eukaryotic kinases that form structurally similar dimers.
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影响因子：
64.5
作者：
Dey, M;Cao, C;Dever, TE
通讯作者：
Dever, TE
影响因子：
2.8
作者：
Dasgupta, A;Datta, P;Basu, J
通讯作者：
Basu, J
影响因子：
13.8
作者：
Crabtree, GR;Schreiber, SL
通讯作者：
Schreiber, SL
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
2.9
作者：
Anderson, Eric;Cole, James L.
通讯作者：
Cole, James L.