Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Sci Adv ; 8(44): eabm4089, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36332013

RESUMO

Enzymatic catalysis is critically dependent on selectivity, active site architecture, and dynamics. To contribute insights into the interplay of these properties, we established an approach with NMR, crystallography, and MD simulations focused on the ubiquitous phosphotransferase adenylate kinase (AK) isolated from Odinarchaeota (OdinAK). Odinarchaeota belongs to the Asgard archaeal phylum that is believed to be the closest known ancestor to eukaryotes. We show that OdinAK is a hyperthermophilic trimer that, contrary to other AK family members, can use all NTPs for its phosphorylation reaction. Crystallographic structures of OdinAK-NTP complexes revealed a universal NTP-binding motif, while 19F NMR experiments uncovered a conserved and rate-limiting dynamic signature. As a consequence of trimerization, the active site of OdinAK was found to be lacking a critical catalytic residue and is therefore considered to be "atypical." On the basis of discovered relationships with human monomeric homologs, our findings are discussed in terms of evolution of enzymatic substrate specificity and cold adaptation.


Assuntos
Adenilato Quinase , Archaea , Humanos , Archaea/genética , Adenilato Quinase/química , Catálise , Domínio Catalítico
2.
Biochemistry ; 58(32): 3408-3412, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31339702

RESUMO

As a key molecule in biology, adenosine triphosphate (ATP) has numerous crucial functions in, for instance, energetics, post-translational modifications, nucleotide biosynthesis, and cofactor metabolism. Here, we have discovered an intricate interplay between the enzyme adenylate kinase and its substrate ATP. The side chain of an arginine residue was found to be an efficient sensor of the aromatic moiety of ATP through the formation of a strong cation-π interaction. In addition to recognition, the interaction was found to have dual functionality. First, it nucleates the activating conformational transition of the ATP binding domain and also affects the specificity in the distant AMP binding domain. In light of the functional consequences resulting from the cation-π interaction, it is possible that the mode of ATP recognition may be a useful tool in enzyme design.


Assuntos
Trifosfato de Adenosina/metabolismo , Adenilato Quinase/metabolismo , Trifosfato de Adenosina/química , Adenilato Quinase/química , Modelos Moleculares , Ligação Proteica , Conformação Proteica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...