Leishmania major biotin protein ligase forms a unique cross-handshake dimer.
Acta Crystallogr D Struct Biol
; 77(Pt 4): 510-521, 2021 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-33825711
ABSTRACT
Biotin protein ligase catalyses the post-translational modification of biotin carboxyl carrier protein (BCCP) domains, a modification that is crucial for the function of several carboxylases. It is a two-step process that results in the covalent attachment of biotin to the ϵ-amino group of a conserved lysine of the BCCP domain of a carboxylase in an ATP-dependent manner. In Leishmania, three mitochondrial enzymes, acetyl-CoA carboxylase, methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase, depend on biotinylation for activity. In view of the indispensable role of the biotinylating enzyme in the activation of these carboxylases, crystal structures of L. major biotin protein ligase complexed with biotin and with biotinyl-5'-AMP have been solved. L. major biotin protein ligase crystallizes as a unique dimer formed by cross-handshake interactions of the hinge region of the two monomers formed by partial unfolding of the C-terminal domain. Interestingly, the substrate (BCCP domain)-binding site of each monomer is occupied by its own C-terminal domain in the dimer structure. This was observed in all of the crystals that were obtained, suggesting a closed/inactive conformation of the enzyme. Size-exclusion chromatography studies carried out using high protein concentrations (0.5â
mM) suggest the formation of a concentration-dependent dimer that exists in equilibrium with the monomer.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Proteínas de Protozoários
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Leishmaniose Cutânea
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Leishmania major
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Carbono-Nitrogênio Ligases
Idioma:
En
Revista:
Acta Crystallogr D Struct Biol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Índia