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| | <StructureSection load='7naa' size='340' side='right'caption='[[7naa]], [[Resolution|resolution]] 2.75Å' scene=''> | | <StructureSection load='7naa' size='340' side='right'caption='[[7naa]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7naa]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NAA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NAA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7naa]] is a 4 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=7NAA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NAA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V17:(4-{[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino}phenyl)[4-(pyrrolidin-1-yl)piperidin-1-yl]methanone'>V17</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pknF_1, pknF, pknF_2, C0094_09540, DSI38_08510, E5M05_19500, E5M52_18375, E5M78_18220, ERS007741_01296, ERS013471_03424, ERS027661_00065, ERS094182_03016, F6W99_00312, FRD82_04005, GCL30_17545, SAMEA2683035_01332 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V17:(4-{[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino}phenyl)[4-(pyrrolidin-1-yl)piperidin-1-yl]methanone'>V17</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7naa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7naa OCA], [https://pdbe.org/7naa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7naa RCSB], [https://www.ebi.ac.uk/pdbsum/7naa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7naa ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7naa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7naa OCA], [https://pdbe.org/7naa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7naa RCSB], [https://www.ebi.ac.uk/pdbsum/7naa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7naa ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PKNF_MYCTU PKNF_MYCTU] Phosphorylates the FHA domains of the ABC transporter Rv1747, the heat-shock protein GroEL 1, and Rv0020c. May play a role in the regulation of glucose transport, cell growth and septum formation.<ref>PMID:15135525</ref> <ref>PMID:15866927</ref> <ref>PMID:15987910</ref> <ref>PMID:19201798</ref> <ref>PMID:21622570</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 7naa" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 7naa" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Balan, A]] | + | [[Category: Balan A]] |
| - | [[Category: Cabarca, S]] | + | [[Category: Cabarca S]] |
| - | [[Category: Counago, R M]] | + | [[Category: Counago RM]] |
| - | [[Category: Oliveira, A A]] | + | [[Category: Oliveira AA]] |
| - | [[Category: Reis, C V.dos]]
| + | [[Category: Takarada JE]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Dos Reis CV]] |
| - | [[Category: Takarada, J E]] | + | |
| - | [[Category: Antimicrobial protein]] | + | |
| - | [[Category: Mtb]]
| + | |
| - | [[Category: Pknf]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Psi-biology]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PKNF_MYCTU Phosphorylates the FHA domains of the ABC transporter Rv1747, the heat-shock protein GroEL 1, and Rv0020c. May play a role in the regulation of glucose transport, cell growth and septum formation.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Mycobacterium tuberculosis (Mtb) has 11 Serine-Threonine Protein Kinases (STPK) that control numerous physiological processes, including cell growth, cell division, metabolic flow, and transcription. PknF is one of the 11 Mtb STPKs that has, among other substrates, two FHA domains (FHA-1 and FHA-2) of the ATP-Binding Cassette (ABC) transporter Rv1747. Phosphorylation in T152 and T210 located in a non-structured linker that connects Rv1747 FHA domains is considerate to be the regulatory mechanism of the transporter. In this work, we resolved the three-dimensional structure of the PknF catalytic domain (cPknF) in complex with the human kinase inhibitor IKK16. cPknF is conserved when compared to other STPKs but shows specific residues in the binding site where the inhibitor is positioned. In addition, using Small Angle X-Ray Scattering analysis we monitored the behavior of the wild type and three FHA-phosphomimetic mutants in solution, and measured the cPknF affinity for these domains. The kinase showed higher affinity for the non-phosphorylated wild type domain and preference for phosphorylation of T152 inducing the rapprochement of the domains and significant structural changes. The results shed some light on the process of regulating the transporter's activity by phosphorylation and arises important questions about evolution and importance of this mechanism for the bacillus.
Structure of the Mycobacterium tuberculosis cPknF and conformational changes induced in forkhead-associated regulatory domains.,Cabarca S, Frazao de Souza M, Albert de Oliveira A, Vignoli Muniz GS, Lamy MT, Vinicius Dos Reis C, Takarada J, Effer B, Souza LS, Iriarte de la Torre L, Counago R, Pinto Oliveira CL, Balan A Curr Res Struct Biol. 2021 Jul 23;3:165-178. doi: 10.1016/j.crstbi.2021.07.001., eCollection 2021. PMID:34382010[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Molle V, Soulat D, Jault JM, Grangeasse C, Cozzone AJ, Prost JF. Two FHA domains on an ABC transporter, Rv1747, mediate its phosphorylation by PknF, a Ser/Thr protein kinase from Mycobacterium tuberculosis. FEMS Microbiol Lett. 2004 May 15;234(2):215-23. doi:, 10.1016/j.femsle.2004.03.033. PMID:15135525 doi:http://dx.doi.org/10.1016/j.femsle.2004.03.033
- ↑ Deol P, Vohra R, Saini AK, Singh A, Chandra H, Chopra P, Das TK, Tyagi AK, Singh Y. Role of Mycobacterium tuberculosis Ser/Thr kinase PknF: implications in glucose transport and cell division. J Bacteriol. 2005 May;187(10):3415-20. PMID:15866927 doi:10.1128/JB.187.10.3415-3420.2005
- ↑ 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
- ↑ Canova MJ, Kremer L, Molle V. The Mycobacterium tuberculosis GroEL1 chaperone is a substrate of Ser/Thr protein kinases. J Bacteriol. 2009 Apr;191(8):2876-83. PMID:19201798 doi:10.1128/JB.01569-08
- ↑ Spivey VL, Molle V, Whalan RH, Rodgers A, Leiba J, Stach L, Walker KB, Smerdon SJ, Buxton RS. Forkhead-associated (FHA) domain containing ABC transporter Rv1747 is positively regulated by Ser/Thr phosphorylation in Mycobacterium tuberculosis. J Biol Chem. 2011 Jul 22;286(29):26198-209. PMID:21622570 doi:10.1074/jbc.M111.246132
- ↑ Cabarca S, Frazao de Souza M, Albert de Oliveira A, Vignoli Muniz GS, Lamy MT, Vinicius Dos Reis C, Takarada J, Effer B, Souza LS, Iriarte de la Torre L, Counago R, Pinto Oliveira CL, Balan A. Structure of the Mycobacterium tuberculosis cPknF and conformational changes induced in forkhead-associated regulatory domains. Curr Res Struct Biol. 2021 Jul 23;3:165-178. doi: 10.1016/j.crstbi.2021.07.001., eCollection 2021. PMID:34382010 doi:http://dx.doi.org/10.1016/j.crstbi.2021.07.001
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