Crystal structure of cystathionine ß-synthase from honeybee Apis mellifera.
J Struct Biol
; 202(1): 82-93, 2018 04.
Article
en En
| MEDLINE
| ID: mdl-29275181
ABSTRACT
Cystathionine ß-synthase (CBS), the key enzyme in the transsulfuration pathway, links methionine metabolism to the biosynthesis of cellular redox controlling molecules. CBS catalyzes the pyridoxal-5'-phosphate-dependent condensation of serine and homocysteine to form cystathionine, which is subsequently converted into cysteine. Besides maintaining cellular sulfur amino acid homeostasis, CBS also catalyzes multiple hydrogen sulfide-generating reactions using cysteine and homocysteine as substrates. In mammals, CBS is activated by S-adenosylmethionine (AdoMet), where it can adopt two different conformations (basal and activated), but exists as a unique highly active species in fruit fly Drosophila melanogaster. Here we present the crystal structure of CBS from honeybey Apis mellifera, which shows a constitutively active dimeric species and let explain why the enzyme is not allosterically regulated by AdoMet. In addition, comparison of available CBS structures unveils a substrate-induced closure of the catalytic cavity, which in humans is affected by the AdoMet-dependent regulation and likely impaired by the homocystinuria causing mutation T191M.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Conformación Proteica
/
Proteínas de Insectos
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Cistationina betasintasa
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Multimerización de Proteína
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Struct Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2018
Tipo del documento:
Article
País de afiliación:
España