FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3021167325> ?p ?o ?g. }

• W3021167325 abstract "Protein Kinases are highly widespread in nature. There are more than 500 protein kinase genes identified representing, more or less, 1.7% of all human genes. They catalyze the protein phosphorylation, a reversible covalent modification that regulates a large number of aspects of cell life: cellular regulation, metabolic pathways, gene transcription, signal transduction,etc. The protein kinase family is large and structurally diverse, but all the enzymes of this group have a highly conserved catalytic core with a bilobal structure that suggests the same catalytic mechanism. For all this reasons, we selected the Protein Kinase A (PKA) as the object of our study, which is the most experimentally studied enzyme of the protein kinase family. Two options have been suggested for the phosphoryl transfer mechanism and up to now it is not clear which of them is the actual one: the first pathway consists in a concerted phosphoryl and proton-transfer process between ATP (the cofactor) and the substrate (always a specific serine, threonine or tyrosine residue); the second one is a dissociative path in which the substrate proton is first accepted by the enzyme's aspartate 166 (Asp166), and then the phosphoryl group passes from ATP to the substrate. Different research groups suggest the second pathway as the most reliable one. We have tested two substrates in this study: the first is the synthetic heptameric peptide, LRRASLG (kemptide), which corresponds to the consensus sequence with a serine at the fifth position (Ser17); the second one is the 20-residue peptide SP20. Both have been modeled in the active center of the PKA enzyme by manually modifying the PKI inhibitor, which is bound to the enzyme in most X-ray structures and in the two structures we selected to build the models. Additionally, we have considered different phosphorylation states of the enzyme (one phosphorylation site modified, two phosphorylation sites modified, or no phosphorylation at all) and a mutant of PKA to test the effect of small modification on the activity of the system. The thermodynamics and kinetics of the PKA-ATP-kemptide complex has been experimentally determined, thus it is, in our opinion, the perfect model to theoretically study which of the pathways is the most favorable. Finally, after an analysis of the behaviour along Molecular Dynamics simulations of the five models we have built, we have selected two of them, thus excluding the SP20 substrate, the mutant, and the deactivated form, to study the potential energy surfaces corresponding to both mechanisms. We have used different techniques and different levels of theory (a modified AM1/d semiempirical method and a DFT method) to achieve optimum results. The semiempirical method choice, followed an accurate analysis of its performance on a rather large set of molecules and model reactions, meant to simulate the phosphorylation reaction catalyzed by the PKA." @default.
• W3021167325 created "2020-05-13" @default.
• W3021167325 creator A5038436777 @default.
• W3021167325 date "2010-01-01" @default.
• W3021167325 modified "2023-09-24" @default.
• W3021167325 title "Dynamics, predicted and not, of a system of biomedical interest: an insight into the pka" @default.
• W3021167325 hasPublicationYear "2010" @default.
• W3021167325 type Work @default.
• W3021167325 sameAs 3021167325 @default.
• W3021167325 citedByCount "0" @default.
• W3021167325 crossrefType "journal-article" @default.
• W3021167325 hasAuthorship W3021167325A5038436777 @default.
• W3021167325 hasConcept C11960822 @default.
• W3021167325 hasConcept C181199279 @default.
• W3021167325 hasConcept C184235292 @default.
• W3021167325 hasConcept C185592680 @default.
• W3021167325 hasConcept C2775880066 @default.
• W3021167325 hasConcept C2776414213 @default.
• W3021167325 hasConcept C55493867 @default.
• W3021167325 hasConcept C62478195 @default.
• W3021167325 hasConcept C86803240 @default.
• W3021167325 hasConcept C87325107 @default.
• W3021167325 hasConcept C97029542 @default.
• W3021167325 hasConceptScore W3021167325C11960822 @default.
• W3021167325 hasConceptScore W3021167325C181199279 @default.
• W3021167325 hasConceptScore W3021167325C184235292 @default.
• W3021167325 hasConceptScore W3021167325C185592680 @default.
• W3021167325 hasConceptScore W3021167325C2775880066 @default.
• W3021167325 hasConceptScore W3021167325C2776414213 @default.
• W3021167325 hasConceptScore W3021167325C55493867 @default.
• W3021167325 hasConceptScore W3021167325C62478195 @default.
• W3021167325 hasConceptScore W3021167325C86803240 @default.
• W3021167325 hasConceptScore W3021167325C87325107 @default.
• W3021167325 hasConceptScore W3021167325C97029542 @default.
• W3021167325 hasLocation W30211673251 @default.
• W3021167325 hasOpenAccess W3021167325 @default.
• W3021167325 hasPrimaryLocation W30211673251 @default.
• W3021167325 hasRelatedWork W1983076247 @default.
• W3021167325 hasRelatedWork W1984717287 @default.
• W3021167325 hasRelatedWork W1990598130 @default.
• W3021167325 hasRelatedWork W2019854154 @default.
• W3021167325 hasRelatedWork W2028172606 @default.
• W3021167325 hasRelatedWork W2040169601 @default.
• W3021167325 hasRelatedWork W2062962548 @default.
• W3021167325 hasRelatedWork W2076227160 @default.
• W3021167325 hasRelatedWork W2078482632 @default.
• W3021167325 hasRelatedWork W2081996981 @default.
• W3021167325 hasRelatedWork W2096980612 @default.
• W3021167325 hasRelatedWork W2105191150 @default.
• W3021167325 hasRelatedWork W2111839632 @default.
• W3021167325 hasRelatedWork W2117501538 @default.
• W3021167325 hasRelatedWork W2120442255 @default.
• W3021167325 hasRelatedWork W2143176665 @default.
• W3021167325 hasRelatedWork W2157418451 @default.
• W3021167325 hasRelatedWork W2175720318 @default.
• W3021167325 hasRelatedWork W2310164309 @default.
• W3021167325 hasRelatedWork W2547741776 @default.
• W3021167325 isParatext "false" @default.
• W3021167325 isRetracted "false" @default.
• W3021167325 magId "3021167325" @default.
• W3021167325 workType "article" @default.