5tvf: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of Trypanosoma brucei AdoMetDC/prozyme heterodimer in complex with inhibitor CGP 40215== | |||
<StructureSection load='5tvf' size='340' side='right' caption='[[5tvf]], [[Resolution|resolution]] 2.42Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5tvf]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TVF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TVF FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CGQ:3-[C-[N-(3-CARBAMIMIDOYL-BENZYLIDENIUM)-HYDRAZINO]-[[AMINOMETHYLIDENE]AMINIUM]-IMINOMETHYL]-BENZAMIDINIUM'>CGQ</scene>, <scene name='pdbligand=PUT:1,4-DIAMINOBUTANE'>PUT</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tvo|5tvo]], [[5tvm|5tvm]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosylmethionine_decarboxylase Adenosylmethionine decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.50 4.1.1.50] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tvf OCA], [http://pdbe.org/5tvf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tvf RCSB], [http://www.ebi.ac.uk/pdbsum/5tvf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tvf ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:27977001</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5tvf" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Adenosylmethionine decarboxylase]] | |||
[[Category: Chen, Z]] | |||
[[Category: Phillips, M A]] | |||
[[Category: Tomchick, D R]] | |||
[[Category: Volkov, O A]] | |||
[[Category: Adometdc]] | |||
[[Category: Allostery]] | |||
[[Category: Cgp40215]] | |||
[[Category: Decarboxylase]] | |||
[[Category: Lyase]] | |||
[[Category: Prozyme]] | |||
[[Category: Pseudoenzyme]] | |||
Revision as of 19:40, 18 January 2017
Crystal structure of Trypanosoma brucei AdoMetDC/prozyme heterodimer in complex with inhibitor CGP 40215Crystal structure of Trypanosoma brucei AdoMetDC/prozyme heterodimer in complex with inhibitor CGP 40215
Structural highlights
Publication Abstract from PubMedCatalytically 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||||