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| - | [[Image:1mru.gif|left|200px]]<br /><applet load="1mru" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1mru, resolution 3.00Å" /> | |
| - | '''Intracellular Ser/Thr protein kinase domain of Mycobacterium tuberculosis PknB.'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Intracellular Ser/Thr protein kinase domain of Mycobacterium tuberculosis PknB.== |
| - | A family of eukaryotic-like Ser/Thr protein kinases occurs in bacteria, but little is known about the structures and functions of these proteins., Here we characterize PknB, a transmembrane signaling kinase from, Mycobacterium tuberculosis. The intracellular PknB kinase domain is active, autonomously, and the active enzyme is phosphorylated on residues, homologous to regulatory phospho-acceptors in eukaryotic Ser/Thr kinases., The crystal structure of the PknB kinase domain in complex with an ATP, analog reveals the active conformation. The predicted fold of the PknB, extracellular domain matches the proposed targeting domain of, penicillin-binding protein 2x. The structural and chemical similarities of, PknB to metazoan homologs support a universal activation mechanism of, Ser/Thr protein kinases in prokaryotes and eukaryotes.
| + | <StructureSection load='1mru' size='340' side='right'caption='[[1mru]], [[Resolution|resolution]] 3.00Å' scene=''> |
| - | | + | == Structural highlights == |
| - | ==About this Structure== | + | <table><tr><td colspan='2'>[[1mru]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MRU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MRU FirstGlance]. <br> |
| - | 1MRU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with MG and AGS as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MRU OCA].
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| - | | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | ==Reference== | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mru OCA], [https://pdbe.org/1mru PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mru RCSB], [https://www.ebi.ac.uk/pdbsum/1mru PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mru ProSAT], [https://www.topsan.org/Proteins/TBSGC/1mru TOPSAN]</span></td></tr> |
| - | Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases., Young TA, Delagoutte B, Endrizzi JA, Falick AM, Alber T, Nat Struct Biol. 2003 Mar;10(3):168-74. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12548283 12548283]
| + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PKNB_MYCTU PKNB_MYCTU] Key component of a signal transduction pathway that regulates cell growth and cell division via phosphorylation of target proteins such as GarA, GlmU, PapA5, PbpA, FhaB (Rv0019c), FhaA (Rv0020c), MviN, PstP, EmbR, Rv1422, Rv1747 and RseA. Shows a strong preference for Thr versus Ser as the phosphoacceptor.<ref>PMID:15985609</ref> <ref>PMID:15978616</ref> <ref>PMID:15987910</ref> <ref>PMID:16817899</ref> <ref>PMID:16980473</ref> <ref>PMID:16436437</ref> <ref>PMID:19826007</ref> <ref>PMID:19121323</ref> <ref>PMID:20025669</ref> <ref>PMID:21423706</ref> <ref>PMID:22275220</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mr/1mru_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1mru ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mycobacterium tuberculosis]] | | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Single protein]]
| + | [[Category: Alber T]] |
| - | [[Category: Alber, T.]] | + | [[Category: Delagoutte B]] |
| - | [[Category: Delagoutte, B.]] | + | [[Category: Endrizzi JA]] |
| - | [[Category: Endrizzi, J.A.]] | + | [[Category: Young TA]] |
| - | [[Category: TBSGC, TB.Structural.Genomics.Consortium.]]
| + | |
| - | [[Category: Young, T.A.]] | + | |
| - | [[Category: AGS]]
| + | |
| - | [[Category: MG]]
| + | |
| - | [[Category: atp-recognition]]
| + | |
| - | [[Category: molecular evolution]]
| + | |
| - | [[Category: protein structure initiative]]
| + | |
| - | [[Category: psi]]
| + | |
| - | [[Category: regulatory]]
| + | |
| - | [[Category: structural genomics]]
| + | |
| - | [[Category: tb structural genomics consortium]]
| + | |
| - | [[Category: tbsgc]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:39:42 2007''
| + | |
| Structural highlights
Function
PKNB_MYCTU Key component of a signal transduction pathway that regulates cell growth and cell division via phosphorylation of target proteins such as GarA, GlmU, PapA5, PbpA, FhaB (Rv0019c), FhaA (Rv0020c), MviN, PstP, EmbR, Rv1422, Rv1747 and RseA. Shows a strong preference for Thr versus Ser as the phosphoacceptor.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Kang CM, Abbott DW, Park ST, Dascher CC, Cantley LC, Husson RN. The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate identification and regulation of cell shape. Genes Dev. 2005 Jul 15;19(14):1692-704. Epub 2005 Jun 28. PMID:15985609 doi:http://dx.doi.org/10.1101/gad.1311105
- ↑ Villarino A, Duran R, Wehenkel A, Fernandez P, England P, Brodin P, Cole ST, Zimny-Arndt U, Jungblut PR, Cervenansky C, Alzari PM. Proteomic identification of M. tuberculosis protein kinase substrates: PknB recruits GarA, a FHA domain-containing protein, through activation loop-mediated interactions. J Mol Biol. 2005 Jul 29;350(5):953-63. PMID:15978616 doi:http://dx.doi.org/10.1016/j.jmb.2005.05.049
- ↑ Grundner C, Gay LM, Alber T. Mycobacterium tuberculosis serine/threonine kinases PknB, PknD, PknE, and PknF phosphorylate multiple FHA domains. Protein Sci. 2005 Jul;14(7):1918-21. PMID:15987910 doi:http://dx.doi.org/10.1110/ps.051413405
- ↑ Sharma K, Gupta M, Krupa A, Srinivasan N, Singh Y. EmbR, a regulatory protein with ATPase activity, is a substrate of multiple serine/threonine kinases and phosphatase in Mycobacterium tuberculosis. FEBS J. 2006 Jun;273(12):2711-21. PMID:16817899 doi:http://dx.doi.org/10.1111/j.1742-4658.2006.05289.x
- ↑ Fernandez P, Saint-Joanis B, Barilone N, Jackson M, Gicquel B, Cole ST, Alzari PM. The Ser/Thr protein kinase PknB is essential for sustaining mycobacterial growth. J Bacteriol. 2006 Nov;188(22):7778-84. Epub 2006 Sep 15. PMID:16980473 doi:http://dx.doi.org/10.1128/JB.00963-06
- ↑ Dasgupta A, Datta P, Kundu M, Basu J. The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division. Microbiology. 2006 Feb;152(Pt 2):493-504. PMID:16436437 doi:http://dx.doi.org/152/2/493
- ↑ Gupta M, Sajid A, Arora G, Tandon V, Singh Y. Forkhead-associated domain-containing protein Rv0019c and polyketide-associated protein PapA5, from substrates of serine/threonine protein kinase PknB to interacting proteins of Mycobacterium tuberculosis. J Biol Chem. 2009 Dec 11;284(50):34723-34. Epub 2009 Oct 13. PMID:19826007 doi:http://dx.doi.org/M109.058834
- ↑ Parikh A, Verma SK, Khan S, Prakash B, Nandicoori VK. PknB-mediated phosphorylation of a novel substrate, N-acetylglucosamine-1-phosphate uridyltransferase, modulates its acetyltransferase activity. J Mol Biol. 2009 Feb 20;386(2):451-64. Epub 2008 Dec 24. PMID:19121323 doi:10.1016/j.jmb.2008.12.031
- ↑ Barik S, Sureka K, Mukherjee P, Basu J, Kundu M. RseA, the SigE specific anti-sigma factor of Mycobacterium tuberculosis, is inactivated by phosphorylation-dependent ClpC1P2 proteolysis. Mol Microbiol. 2010 Feb;75(3):592-606. doi: 10.1111/j.1365-2958.2009.07008.x., Epub 2009 Dec 16. PMID:20025669 doi:http://dx.doi.org/10.1111/j.1365-2958.2009.07008.x
- ↑ Sajid A, Arora G, Gupta M, Upadhyay S, Nandicoori VK, Singh Y. Phosphorylation of Mycobacterium tuberculosis Ser/Thr phosphatase by PknA and PknB. PLoS One. 2011 Mar 9;6(3):e17871. doi: 10.1371/journal.pone.0017871. PMID:21423706 doi:http://dx.doi.org/10.1371/journal.pone.0017871
- ↑ Gee CL, Papavinasasundaram KG, Blair SR, Baer CE, Falick AM, King DS, Griffin JE, Venghatakrishnan H, Zukauskas A, Wei JR, Dhiman RK, Crick DC, Rubin EJ, Sassetti CM, Alber T. A phosphorylated pseudokinase complex controls cell wall synthesis in mycobacteria. Sci Signal. 2012 Jan 24;5(208):ra7. PMID:22275220 doi:10.1126/scisignal.2002525
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