Identification of general acid catalyst for the ATPase activity of Lynch syndrome-related MutL homologs
Fukui, K.; Fujii, Y.; Yano, T.
Show abstract
Mutations of mismatch repair MutL homologs are causative of a hereditary cancer, Lynch syndrome. Investigation of MutL facilitates genetic diagnoses essential for cancer risk managements and therapies. We characterized MutL homologs from human and a hyperthermophile, Aquifex aeolicus, (aqMutL) to reveal the catalytic mechanism for the ATPase activity. Although existence of a general acid catalyst had not been conceived in the mechanism, analysis of the pH dependence of the aqMutL ATPase activity revealed that the reaction is accelerated by general acid-base catalysis. Analyses of mutant aqMutLs showed that Lys79 is the general acid, and the corresponding residues were confirmed to be critical for activities of human homologs, on the basis of which a catalytic mechanism for MutL ATPase is proposed. These and other results described here would contribute to evaluating the pathogenicity of Lynch syndrome-associated missense mutations.
Matching journals
The top 2 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- The PqsE active site as a target for small molecule antimicrobial agents against Pseudomonas aeruginosa 93%
- Comparative analysis of CPI-motif regulation of biochemical functions of actin capping protein 93%
- What drives chorismate mutase to top performance? Insights from a combined in silico and in vitro study 93%
Similar papers in this journal
- RudS: Bacterial Desulfidase Responsible for tRNA 4-Thiouridine De-modification 95%
- Structural and functional characterization of DdrC, a novel DNA damage-induced nucleoid associated protein involved in DNA compaction 94%
- A transfer RNA methyltransferase with an unusual domain composition catalyzes 2'-O-methylation at position 6 in tRNA 94%
Similar papers in this journal
- Biophysical and biochemical evidence for the role of acetate kinases (AckAs) in an acetogenic pathway in pathogenic spirochetes 94%
- The AMP deaminase of the mollusk Helix pomatia is an unexpected member of the adenosine deaminase-related growth factor (ADGF) family 94%
- Larger active site in an ancestral hydroxynitrile lyase increases catalytically promiscuous esterase activity 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.