PDBsum entry 2luo

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Hydrolase PDB id
Protein chain
164 a.a.
PDB id:
Name: Hydrolase
Title: Nmr solution structure of apo-mptpa
Structure: Low molecular weight protein-tyrosine-phosphatase chain: a. Synonym: ptpase. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: ptpa, rv2234, mt2293, mtcy427.15. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: plyss. Other_details: original pet16btev vector was double ncoi/bl digested and cloned into the modified pkm263 (6xhis tag pro between nde1 and xho1) vector
NMR struc: 20 models
Authors: T.Stehle,S.Sreeramulu,F.Loehr,C.Richter,K.Saxena,H.R.A.Jonke H.Schwalbe
Key ref: T.Stehle et al. (2012). 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, 287, 34569-34582. PubMed id: 22888002 DOI: 10.1074/jbc.M112.399261
19-Jun-12     Release date:   15-Aug-12    
Go to PROCHECK summary

Protein chain
P9WIA1  (PTPA_MYCTU) -  Probable low molecular weight protein-tyrosine-phosphatase
163 a.a.
164 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     host cell endosome   3 terms 
  Biological process     peptidyl-tyrosine dephosphorylation   3 terms 
  Biochemical function     hydrolase activity     3 terms  


DOI no: 10.1074/jbc.M112.399261 J Biol Chem 287:34569-34582 (2012)
PubMed id: 22888002  
The apo-structure of the low molecular weight protein-tyrosine phosphatase A (MptpA) from Mycobacterium tuberculosis allows for better target-specific drug development.
T.Stehle, S.Sreeramulu, F.Löhr, C.Richter, K.Saxena, H.R.Jonker, H.Schwalbe.
Protein-tyrosine phosphatases (PTPs) and protein-tyrosine kinases co-regulate cellular processes. In pathogenic bacteria, they are frequently exploited to act as key virulence factors for human diseases. Mycobacterium tuberculosis, the causative organism of tuberculosis, secretes a low molecular weight PTP (LMW-PTP), MptpA, which is required for its survival upon infection of host macrophages. Although there is otherwise no sequence similarity of LMW-PTPs to other classes of PTPs, the phosphate binding loop (P-loop) CX(5)R and the loop containing a critical aspartic acid residue (D-loop), required for the catalytic activity, are well conserved. In most high molecular weight PTPs, ligand binding to the P-loop triggers a large conformational reorientation of the D-loop, in which it moves ∼10 Å, from an "open" to a "closed" conformation. Until now, there have been no ligand-free structures of LMW-PTPs described, and hence the dynamics of the D-loop have remained largely unknown for these PTPs. Here, we present a high resolution solution NMR structure of the free form of the MptpA LMW-PTP. In the absence of ligand and phosphate ions, the D-loop adopts an open conformation. Furthermore, we characterized the binding site of phosphate, a competitive inhibitor of LMW-PTPs, on MptpA and elucidated the involvement of both the P- and D-loop in phosphate binding. Notably, in LMW-PTPs, the phosphorylation status of two well conserved tyrosine residues, typically located in the D-loop, regulates the enzyme activity. PtkA, the kinase complementary to MptpA, phosphorylates these two tyrosine residues in MptpA. We characterized the MptpA-PtkA interaction by NMR spectroscopy to show that both the P- and D-loop form part of the binding interface.