4wp8 | pdb_00004wp8

Crystal structure of Adenylyl cyclase Ma1120 from Mycobacterium Avium in complex with 2'5'-DD-3'-ATP and Manganese ion

spinqualitylabelsall models 4wp8, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4wp8 is a 2 chain structure with sequence from Mycobacterium avium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.65Å Ligands: CL, MN, ZDA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5UFR5_MYCAV Publication Abstract from PubMed An adenylyl cyclase from Mycobacterium avium, Ma1120, is a functional orthologue of a pseudogene Rv1120c from Mycobacterium tuberculosis. We report the crystal structure of Ma1120 in a monomeric form and its truncated construct as a dimer. Ma1120 exists as a monomer in solution and crystallized as a monomer in the absence of substrate or inhibitor. An additional alpha-helix present at the N-terminus of the monomeric structure blocks the active site by interacting with the substrate binding residues and occupying the dimer interface region. However, the enzyme has been found to be active in solution, indicating the movement of the helix away from the interface to facilitate the formation of active dimers in conditions favourable for catalysis. Thus, the N-terminal helix of Ma1120 keeps the enzyme in an autoinhibited state when it is not active. Deletion of this helix enabled us to crystallize the molecule as an active homodimer in the presence of a P-site inhibitor 2',5'-dideoxy-3'-ATP, or pyrophosphate along with metal ions. The substrate specifying lysine residue plays a dual role of interacting with the substrate and stabilizing the dimer. The dimerization loop region harbouring the second substrate specifying residue, an aspartate, shows significant differences in conformation and position between the monomeric and dimeric structures. Thus, this study has not only revealed that significant structural transitions are required for the interconversion of the inactive and the active forms of the enzyme, but also provided precise nature of these transitions. Autoinhibitory mechanism and activity-related structural changes in a mycobacterial adenylyl cyclase.,Barathy DV, Bharambe NG, Syed W, Zaveri A, Visweswariah SS, Colavarsigmao M, Misquith S, Suguna K J Struct Biol. 2015 Jun;190(3):304-13. doi: 10.1016/j.jsb.2015.04.013. Epub 2015 , Apr 24. PMID:25916753 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 3D Adenylyl cyclase 3D structures

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