CysE and CysK, the last two enzymes of the cysteine biosynthetic pathway, engage in a bienzyme complex, cysteine synthase, with yet incompletely characterized three-dimensional structure and regulatory function. Being absent in mammals, the two enzymes and their complex are attractive targets for antibacterial drugs. We have used hydrogen/deuterium exchange MS to unveil how complex formation affects the conformational dynamics of CysK and CysE. Our results support a model where CysE is present in solution as a dimer of trimers, and each trimer can bind one CysK homodimer. When CysK binds to one CysE monomer, intratrimer allosteric communication ensures conformational and dynamic symmetry within the trimer. Furthermore, a long-range allosteric signal propagates through CysE to induce stabilization of the interface between the two CysE trimers, preparing the second trimer for binding the second CysK with a nonrandom orientation. These results provide new molecular insights into the allosteric formation of the cysteine synthase complex and could help guide antibacterial drug design.

Revealing the dynamic allosteric changes required for formation of the cysteine synthase complex by hydrogen-deuterium exchange MS / Rosa, B.; Dickinson, E. R.; Marchetti, M.; Campanini, B.; Pioselli, B.; Bettati, S.; Rand, K. D.. - In: MOLECULAR & CELLULAR PROTEOMICS. - ISSN 1535-9476. - 20(2021). [10.1016/j.mcpro.2021.100098]

Revealing the dynamic allosteric changes required for formation of the cysteine synthase complex by hydrogen-deuterium exchange MS

Rosa B.;Marchetti M.;Campanini B.;Bettati S.;
2021

Abstract

CysE and CysK, the last two enzymes of the cysteine biosynthetic pathway, engage in a bienzyme complex, cysteine synthase, with yet incompletely characterized three-dimensional structure and regulatory function. Being absent in mammals, the two enzymes and their complex are attractive targets for antibacterial drugs. We have used hydrogen/deuterium exchange MS to unveil how complex formation affects the conformational dynamics of CysK and CysE. Our results support a model where CysE is present in solution as a dimer of trimers, and each trimer can bind one CysK homodimer. When CysK binds to one CysE monomer, intratrimer allosteric communication ensures conformational and dynamic symmetry within the trimer. Furthermore, a long-range allosteric signal propagates through CysE to induce stabilization of the interface between the two CysE trimers, preparing the second trimer for binding the second CysK with a nonrandom orientation. These results provide new molecular insights into the allosteric formation of the cysteine synthase complex and could help guide antibacterial drug design.
Revealing the dynamic allosteric changes required for formation of the cysteine synthase complex by hydrogen-deuterium exchange MS / Rosa, B.; Dickinson, E. R.; Marchetti, M.; Campanini, B.; Pioselli, B.; Bettati, S.; Rand, K. D.. - In: MOLECULAR & CELLULAR PROTEOMICS. - ISSN 1535-9476. - 20(2021). [10.1016/j.mcpro.2021.100098]
File in questo prodotto:
File Dimensione Formato  
Mol Cell Proteomics 2021, 20, 100098.pdf

accesso aperto

Descrizione: Articolo principale
Tipologia: Versione (PDF) editoriale
Licenza: Creative commons
Dimensione 2.24 MB
Formato Adobe PDF
2.24 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2897516
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact