Structural insight into the effect of polymorphic variation on the functional dynamics of methionine synthase reductase: Implications in neural tube defects.
Chem Biol Drug Des
; 97(2): 283-292, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-32812692
ABSTRACT
Neural tube defects (NTDs), one of the most common birth defects, are strongly associated with the variations of several single nucleotide polymorphisms (SNPs) in the MTRR gene. The gene codes a key enzyme that is involved in the rejuvenation of methionine synthase activity. An allelic variant of the protein leads to missense mutation at 49th position from isoleucine to methionine (I49M) is associated with higher disease prevalence in different populations. Here, extensive molecular dynamics simulations and interaction network analysis reveal that the 49th isoleucine is a crucial residue that allosterically regulates the dynamics between the flavin mononucleotide (FMN) and NADP(H) binding domains. I49M variation alters the functional dynamics in a way that might impede the electron transport chain along the NADP(H) â flavin adenine dinucleotide â FMN pathway. The present study provides functional insights into the effect of the genetic variations of the MTRR gene on the NTDs disease pathogenesis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ferredoxina-NADP Redutase
/
Defeitos do Tubo Neural
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Chem Biol Drug Des
Assunto da revista:
BIOQUIMICA
/
FARMACIA
/
FARMACOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Índia