2luo

NMR solution structure of apo-MptpANMR solution structure of apo-MptpA

Structural highlights 2luo is a 1 chain structure with sequence from Mycobacterium tuberculosis. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PTPA_MYCTU Mediates host-pathogen interaction and interferes with vesicular trafficking in the infected macrophage. Inhibits host phagolysosomal fusion in M.tuberculosis-infected macrophages to promote bacteria survival. Dephosphorylates host VPS33B protein, which induces a block of the host phagosome maturation within macrophage cells. Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates. Publication Abstract from PubMed Protein tyrosine phosphatases and kinases (PTPs and PTKs) co-regulate cellular processes. In pathogenic bacteria, they are frequently exploited to act as key virulence factors for human diseases. Mycobacterium tuberculosis (Mtb), the causative organism of tuberculosis (TB), secretes a low-molecular-weight (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) CX5R and the loop containing a critical aspartic acid residue (D-loop), required for the catalytic activity, are well conserved. In most high-molecular-weight (HMW)-PTPs, ligand binding to the P-loop triggers a large conformational reorientation of the D-loop, in which it moves ~10 A, 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 has 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 P- and D-loop form part of the binding interface. The apo-structure of the low-molecular-weight protein tyrosine phosphatase A (MptpA) from Mycobacterium tuberculosis allows for better target-specific drug development.,Stehle T, Sreeramulu S, Lohr F, Richter C, Saxena K, Jonker HR, Schwalbe H J Biol Chem. 2012 Aug 10. PMID:22888002 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tyrosine phosphatase 3D structures

spinqualitylabelsall models 2luo Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image