Crystal structure of cystathionine β-synthase from honeybee Apis mellifera

Autor: Jan P. Kraus, Paula Giménez-Mascarell, Tomas Majtan, June Ereño-Orbea, Juraj Majtan, Jaroslav Klaudiny, Luis Alfonso Martínez-Cruz, Iker Oyenarte
Rok vydání: 2018
Předmět:
Models
Molecular
60107 Enzymes
inorganic chemicals
0301 basic medicine
S-Adenosylmethionine
60199 Biochemistry and Cell Biology not elsewhere classified
congenital
hereditary
and neonatal diseases and abnormalities
Homocysteine
Protein Conformation
Biophysics
Cystathionine beta-Synthase
Transsulfuration
Homocystinuria
Transsulfuration pathway
Crystallography
X-Ray
Substrate Specificity
Serine
03 medical and health sciences
chemistry.chemical_compound
Structural Biology
medicine
Animals
Humans
Amino Acid Sequence
Cysteine
Molecular Biology
Cysteine metabolism
Sequence Homology
Amino Acid
biology
Chemistry
nutritional and metabolic diseases
Bees
medicine.disease
Cystathionine beta synthase
030104 developmental biology
Biochemistry
FOS: Biological sciences
biology.protein
Insect Proteins
Protein Multimerization
Zdroj: Journal of Structural Biology. 202:82-93
ISSN: 1047-8477
DOI: 10.1016/j.jsb.2017.12.008
Popis: Cystathionine β-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.
Databáze: OpenAIRE
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