6F2X

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


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: target function 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

The domain architecture of PtkA, the first tyrosine kinase fromMycobacterium tuberculosis, differs from the conventional kinase architecture.

Niesteruk, A.Jonker, H.R.A.Richter, C.Linhard, V.Sreeramulu, S.Schwalbe, H.

(2018) J Biol Chem 293: 11823-11836

  • DOI: https://doi.org/10.1074/jbc.RA117.000120
  • Primary Citation of Related Structures:  
    6F2X

  • PubMed Abstract: 

    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 intrinsically disordered domain (IDD PtkA ) and the C-terminal rigid kinase core domain (KCD PtkA ). The interaction between the two domains, together with the structural model of the complex proposed in this study, reveal that the IDD PtkA is unstructured and highly dynamic, allowing for a "fly-casting-like" mechanism of transient interactions with the rigid KCD PtkA This interaction modulates the accessibility of the KCD PtkA active site. In general, the structural and functional knowledge of PtkA gained in this study is crucial for understanding the MptpA-PtkA interactions, the catalytic mechanism, and the role of the kinase-phosphatase regulatory system in Mtb virulence.


  • Organizational Affiliation

    From the Institute for Organic Chemistry and Chemical Biology, Centre for Biomolecular Magnetic Resonance (BMRZ), Goethe-University Frankfurt am Main, Max-von-Laue-Strasse 7, D-60438 Frankfurt am Main, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein Tyrosine Kinase A216Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: Rv2232MTCY427.13/MTCY427.14
UniProt
Find proteins for P9WPI9 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WPI9 
Go to UniProtKB:  P9WPI9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WPI9
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: target function 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
German Research FoundationGermanyMacromolecular Complexes
European CommissioniNext - 653706
State of HesseGermanyBMRZ

Revision History  (Full details and data files)

  • Version 1.0: 2018-07-04
    Type: Initial release
  • Version 1.1: 2018-08-08
    Changes: Data collection, Database references
  • Version 1.2: 2019-05-08
    Changes: Data collection
  • Version 1.3: 2019-09-11
    Changes: Data collection
  • Version 1.4: 2023-06-14
    Changes: Database references, Other