5TVF

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

Summary for 5TVF

• Entry DOI: 10.2210/pdb5tvf/pdb
• Related: 5TVM 5TVO
• Descriptor: S-adenosylmethionine decarboxylase beta chain, S-adenosylmethionine decarboxylase alpha chain, S-adenosylmethionine decarboxylase proenzyme-like, putative, ... (7 entities in total)
• Functional Keywords: adometdc, cgp40215, decarboxylase, allostery, pseudoenzyme, prozyme, lyase
• Biological source: Trypanosoma brucei brucei (strain 927/4 GUTat10.1); More
• Total number of polymer chains: 6
• Total formula weight: 157901.74

Authors

Phillips, M.A.,Volkov, O.A.,Chen, Z.,Tomchick, D.R. (deposition date: 2016-11-08, release date: 2017-01-11, Last modification date: 2024-10-23)

Primary citation

Volkov, O.A.,Kinch, L.,Ariagno, C.,Deng, X.,Zhong, S.,Grishin, N.,Tomchick, D.R.,Chen, Z.,Phillips, M.A.
Relief of autoinhibition by conformational switch explains enzyme activation by a catalytically dead paralog.
Elife, 5:-, 2016

PubMed Abstract: 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 -adenosylmethionine decarboxylase alone and in functional complex with its catalytically dead paralogous partner, prozyme. We show monomeric AdoMetDC 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 -to- proline isomerization, reorganization of a β-sheet, and insertion of the N-terminal α-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.

PubMed: 27977001
DOI: 10.7554/eLife.20198

Experimental method

X-RAY DIFFRACTION (2.42 Å)