Allosteric mechanism of pyruvate kinase from Leishmania mexicana uses a rock and lock model.
J Biol Chem
; 285(17): 12892-8, 2010 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-20123988
Allosteric regulation provides a rate management system for enzymes involved in many cellular processes. Ligand-controlled regulation is easily recognizable, but the underlying molecular mechanisms have remained elusive. We have obtained the first complete series of allosteric structures, in all possible ligated states, for the tetrameric enzyme, pyruvate kinase, from Leishmania mexicana. The transition between inactive T-state and active R-state is accompanied by a simple symmetrical 6 degrees rigid body rocking motion of the A- and C-domain cores in each of the four subunits. However, formation of the R-state in this way is only part of the mechanism; eight essential salt bridge locks that form across the C-C interface provide tetramer rigidity with a coupled 7-fold increase in rate. The results presented here illustrate how conformational changes coupled with effector binding correlate with loss of flexibility and increase in thermal stability providing a general mechanism for allosteric control.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piruvato Quinase
/
Leishmania mexicana
/
Modelos Moleculares
/
Proteínas de Protozoários
/
Modelos Químicos
Limite:
Animals
País/Região como assunto:
Mexico
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Reino Unido
País de publicação:
Estados Unidos