5tvf

Crystal structure of Trypanosoma brucei AdoMetDC/prozyme heterodimer in complex with inhibitor CGP 40215

spinqualitylabelsall models 5tvf, resolution 2.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5tvf is a 6 chain structure with sequence from Trypanosoma brucei brucei TREU927. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.42Å Ligands: B3P, CGQ, PUT, PYR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q587A7_TRYB2 Publication Abstract from PubMed Catalytically inactive enzyme paralogs occur in many genomes. Some regulate their active counterparts but the structural principles of this regulation remain largely unknown. We report X-ray structures of Trypanosoma brucei S-adenosylmethionine decarboxylase alone and in functional complex with its catalytically dead paralogous partner, prozyme. We show monomeric TbAdoMetDC is inactive because of autoinhibition by its N-terminal sequence. Heterodimerization with prozyme displaces this sequence from the active site through a complex mechanism involving a cis-to-trans proline isomerization, reorganization of a beta-sheet, and insertion of the N-terminal alpha-helix into the heterodimer interface, leading to enzyme activation. We propose that the evolution of this intricate regulatory mechanism was facilitated by the acquisition of the dimerization domain, a single step that can in principle account for the divergence of regulatory schemes in the AdoMetDC enzyme family. These studies elucidate an allosteric mechanism in an enzyme and a plausible scheme by which such complex cooperativity evolved. Relief of autoinhibition by conformational switch explains enzyme activation by a catalytically dead paralog.,Volkov OA, Kinch L, Ariagno C, Deng X, Zhong S, Grishin N, Tomchick DR, Chen Z, Phillips MA Elife. 2016 Dec 15;5. pii: e20198. doi: 10.7554/eLife.20198. PMID:27977001 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also SAM decarboxylase

Proteopedia Page Contributors and Editors (what is this?)

OCA