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6f2x

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Structural characterization of the Mycobacterium tuberculosis Protein Tyrosine Kinase A (PtkA)

Structural highlights

6f2x is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PTKA_MYCTU Required for growth within macrophages (PubMed:29317718). Catalyzes the phosphorylation of PtpA on the tyrosine residues at positions 128 and 129, thereby increasing PtpA phosphatase activity and promoting pathogenicity (PubMed:19366344, PubMed:22888002, PubMed:25535696, PubMed:29724125). Also phosphorylates the thioredoxin reductase TrxB (PubMed:29317718).^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The discovery that MptpA (low-molecular-weight protein tyrosine phosphatase A) from Mycobacterium tuberculosis (Mtb) has an essential role for Mtb virulence has motivated research of tyrosine-specific phosphorylation in Mtb and other pathogenic bacteria. The phosphatase activity of MptpA is regulated via phosphorylation on Tyr-128 and Tyr-129. Thus far, only a single tyrosine-specific kinase, protein tyrosine kinase A (PtkA), encoded by the Rv2232 gene has been identified within the Mtb genome. MptpA undergoes phosphorylation by PtkA. PtkA is an atypical bacterial tyrosine kinase, as its sequence differs from the sequence consensus within this family. The lack of structural information on PtkA hampers the detailed characterization of the MptpA-PtkA interaction. Here, using NMR spectroscopy, we provide a detailed structural characterization of the PtkA architecture and describe its intra- and intermolecular interactions with MptpA. We found that PtkA's domain architecture differs from the conventional kinase architecture and is composed of two domains, the N-terminal highly flexible IDDPtkA and the C-terminal rigid KCDPtkA The interaction studies between the two domains together with the structural model of the IDD-KCD complex proposed in this study reveals that the IDD is unstructured and highly dynamic, allowing for a "fly-casting" like mechanism of transient interactions with the rigid KCD. This interaction modulates the accessibility of the KCD active site. In general, the structural and functional knowledge of PtkA gained in this study, is crucial for understanding the MptpA-PtkA interactions, catalytic mechanism and the role of kinase-phosphatase regulatory system in Mtb virulence.

The domain architecture of the PtkA, the first tyrosine kinase from Mycobacterium tuberculosis differs from the conventional kinase architecture.,Niesteruk A, Jonker HRA, Richter C, Linhard V, Sreeramulu S, Schwalbe H J Biol Chem. 2018 Jun 8. pii: RA117.000120. doi: 10.1074/jbc.RA117.000120. PMID:29884774^[6]

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

References

↑ Bach H, Wong D, Av-Gay Y. Mycobacterium tuberculosis PtkA is a novel protein tyrosine kinase whose substrate is PtpA. Biochem J. 2009 May 13;420(2):155-60. PMID:19366344 doi:10.1042/BJ20090478
↑ Stehle T, Sreeramulu S, Lohr F, Richter C, Saxena K, Jonker HR, Schwalbe H. The apo-structure of the low-molecular-weight protein tyrosine phosphatase A (MptpA) from Mycobacterium tuberculosis allows for better target-specific drug development. J Biol Chem. 2012 Aug 10. PMID:22888002 doi:10.1074/jbc.M112.399261
↑ Zhou P, Li W, Wong D, Xie J, Av-Gay Y. Phosphorylation control of protein tyrosine phosphatase A activity in Mycobacterium tuberculosis. FEBS Lett. 2015 Jan 30;589(3):326-31. PMID:25535696 doi:10.1016/j.febslet.2014.12.015
↑ Wong D, Li W, Chao JD, Zhou P, Narula G, Tsui C, Ko M, Xie J, Martinez-Frailes C, Av-Gay Y. Protein tyrosine kinase, PtkA, is required for Mycobacterium tuberculosis growth in macrophages. Sci Rep. 2018 Jan 9;8(1):155. PMID:29317718 doi:10.1038/s41598-017-18547-9
↑ Jaiswal S, Chatterjee A, Pandey S, Lata K, Gadi RK, Manda R, Kumar S, Reddy MS, Ramachandran R, Srivastava KK. Mycobacterial protein tyrosine kinase, PtkA phosphorylates PtpA at tyrosine residues and the mechanism is stalled by the novel series of inhibitors. J Drug Target. 2019 Jan;27(1):51-59. PMID:29724125 doi:10.1080/1061186X.2018.1473407
↑ Niesteruk A, Jonker HRA, Richter C, Linhard V, Sreeramulu S, Schwalbe H. The domain architecture of the PtkA, the first tyrosine kinase from Mycobacterium tuberculosis differs from the conventional kinase architecture. J Biol Chem. 2018 Jun 8. pii: RA117.000120. doi: 10.1074/jbc.RA117.000120. PMID:29884774 doi:http://dx.doi.org/10.1074/jbc.RA117.000120

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6f2x"

@@ Line 1: / Line 1: @@
 ==Structural characterization of the Mycobacterium tuberculosis Protein Tyrosine Kinase A (PtkA)==
-<StructureSection load='6f2x' size='340' side='right'caption='[[6f2x]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='6f2x' size='340' side='right'caption='[[6f2x]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6f2x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F2X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F2X FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6f2x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6F2X FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rv2232, MTCY427.13/MTCY427.14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
+</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=6f2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f2x OCA], [https://pdbe.org/6f2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6f2x RCSB], [https://www.ebi.ac.uk/pdbsum/6f2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6f2x ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6f2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f2x OCA], [http://pdbe.org/6f2x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f2x RCSB], [http://www.ebi.ac.uk/pdbsum/6f2x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f2x ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/PTKA_MYCTU PTKA_MYCTU] Required for growth within macrophages (PubMed:29317718). Catalyzes the phosphorylation of PtpA on the tyrosine residues at positions 128 and 129, thereby increasing PtpA phosphatase activity and promoting pathogenicity (PubMed:19366344, PubMed:22888002, PubMed:25535696, PubMed:29724125). Also phosphorylates the thioredoxin reductase TrxB (PubMed:29317718).<ref>PMID:19366344</ref> <ref>PMID:22888002</ref> <ref>PMID:25535696</ref> <ref>PMID:29317718</ref> <ref>PMID:29724125</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 ==See Also==
-*[[Tyrosine kinase|Tyrosine kinase]]
+*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
 == References ==
 <references/>
@@ Line 24: / Line 25: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Myctu]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Hutchison, M]]
+[[Category: Hutchison M]]
-[[Category: Jonker, H R.A]]
+[[Category: Jonker HRA]]
-[[Category: Linhard, V]]
+[[Category: Linhard V]]
-[[Category: Niesteruk, A]]
+[[Category: Niesteruk A]]
-[[Category: Richter, C]]
+[[Category: Richter C]]
-[[Category: Schwalbe, H]]
+[[Category: Schwalbe H]]
-[[Category: Sreeramulu, S]]
+[[Category: Sreeramulu S]]
-[[Category: Transferase]]
-[[Category: Tyrosine kinase phosphorylation mycobacterium tuberculosis]]

6f2x

From Proteopedia

Current revision

Structural characterization of the Mycobacterium tuberculosis Protein Tyrosine Kinase A (PtkA)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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