FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2060370337> ?p ?o ?g. }

• W2060370337 endingPage "485" @default.
• W2060370337 startingPage "478" @default.
• W2060370337 abstract "Many Gram-positive pathogens possess external pili or fimbriae with which they adhere to host cells during the infection process. Unusual dual intramolecular isopeptide bonds between Asn and Lys side chains within the N-terminal and C-terminal domains of the pilus subunits have been observed initially in the Streptococcus pyogenes pilin subunit Spy0128 and subsequently in GBS52 from Streptococcus agalactiae, in the BcpA major pilin of Bacillus cereus and in the RrgB pilin of Streptococcus pneumoniae, among others. Within each pilin subunit, intramolecular isopeptide bonds serve to stabilize the protein. These bonds provide a means to withstand large external mechanical forces, as well as possibly assisting in supporting a conformation favored for pilin subunit polymerization via sortase transpeptidases. Genome-wide analyses of pili-containing Gram-positive bacteria are known or suspected to contain isopeptide bonds in pilin subunits. For the autocatalytic formation of isopeptide cross-links, a conservation of three amino acids including Asn, Lys, and a catalytically important acidic Glu (or Asp) residue are responsible. However, the chemical mechanism of how isopeptide bonds form within pilin remains poorly understood. Although it is possible that several mechanistic paths could lead to isopeptide bond formation in pili, the requirement of a conserved glutamate and highly organized positioning of residues within the hydrophobic environment of the active site were found in numerous pilin crystal structures such as Spy0128 and RrgB. This suggests a mechanism involving direct coupling of lysine side chain amine to the asparagine carboxamide mediated by critical acid/base or hydrogen bonding interactions with the catalytic glutamate residue. From this mechanistic perspective, we used the QM/MM minimum free-energy path method to examine the reaction details of forming the isopeptide bonds with Spy0128 as a model pilin, specifically focusing on the role of the glutamate in catalysis. It was determined that the reaction mechanism likely consists of two major steps: the nucleophilic attack on Cγ by nitrogen in the unprotonated Lys ε-amino group and, then two concerted proton transfers occur during the formation of the intramolecular isopeptide bond to subsequently release ammonia. More importantly, within the dual active sites of Spy0128, Glu117, and Glu258 residues function as crucial catalysts for each isopeptide bond formation, respectively, by relaying two proton transfers. This work also suggests that domain−domain interactions within Spy0128 may modulate the reactivity of residues within each active site. Our results may hopefully shed light on the molecular mechanisms of pilin biogenesis in Gram-positive bacteria." @default.
• W2060370337 created "2016-06-24" @default.
• W2060370337 creator A5012313601 @default.
• W2060370337 creator A5017472831 @default.
• W2060370337 creator A5019365851 @default.
• W2060370337 creator A5030709088 @default.
• W2060370337 creator A5057655602 @default.
• W2060370337 creator A5091830603 @default.
• W2060370337 date "2010-12-13" @default.
• W2060370337 modified "2023-10-10" @default.
• W2060370337 title "Autocatalytic Intramolecular Isopeptide Bond Formation in Gram-Positive Bacterial Pili: A QM/MM Simulation" @default.
• W2060370337 cites W1482392342 @default.
• W2060370337 cites W1504277857 @default.
• W2060370337 cites W1550209178 @default.
• W2060370337 cites W1561893393 @default.
• W2060370337 cites W1646690512 @default.
• W2060370337 cites W1832030339 @default.
• W2060370337 cites W1892184508 @default.
• W2060370337 cites W1968530497 @default.
• W2060370337 cites W1972435468 @default.
• W2060370337 cites W1976499671 @default.
• W2060370337 cites W1979766691 @default.
• W2060370337 cites W1995478193 @default.
• W2060370337 cites W1999572189 @default.
• W2060370337 cites W1999818041 @default.
• W2060370337 cites W2011134566 @default.
• W2060370337 cites W2011225686 @default.
• W2060370337 cites W2019500447 @default.
• W2060370337 cites W2023271753 @default.
• W2060370337 cites W2025421399 @default.
• W2060370337 cites W2027408247 @default.
• W2060370337 cites W2035266068 @default.
• W2060370337 cites W2038417675 @default.
• W2060370337 cites W2038533471 @default.
• W2060370337 cites W2038551788 @default.
• W2060370337 cites W2039817895 @default.
• W2060370337 cites W2052339307 @default.
• W2060370337 cites W2052397091 @default.
• W2060370337 cites W2056680298 @default.
• W2060370337 cites W2057228803 @default.
• W2060370337 cites W2065815743 @default.
• W2060370337 cites W2067174909 @default.
• W2060370337 cites W2074986801 @default.
• W2060370337 cites W2075753195 @default.
• W2060370337 cites W2086957099 @default.
• W2060370337 cites W2087180492 @default.
• W2060370337 cites W2091620265 @default.
• W2060370337 cites W2104725270 @default.
• W2060370337 cites W2105021118 @default.
• W2060370337 cites W2106140689 @default.
• W2060370337 cites W2115453381 @default.
• W2060370337 cites W2124704072 @default.
• W2060370337 cites W2131209038 @default.
• W2060370337 cites W2143981217 @default.
• W2060370337 cites W2150931072 @default.
• W2060370337 cites W2152220941 @default.
• W2060370337 doi "https://doi.org/10.1021/ja107513t" @default.
• W2060370337 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3081525" @default.
• W2060370337 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21142157" @default.
• W2060370337 hasPublicationYear "2010" @default.
• W2060370337 type Work @default.
• W2060370337 sameAs 2060370337 @default.
• W2060370337 citedByCount "33" @default.
• W2060370337 countsByYear W20603703372012 @default.
• W2060370337 countsByYear W20603703372013 @default.
• W2060370337 countsByYear W20603703372014 @default.
• W2060370337 countsByYear W20603703372015 @default.
• W2060370337 countsByYear W20603703372016 @default.
• W2060370337 countsByYear W20603703372017 @default.
• W2060370337 countsByYear W20603703372020 @default.
• W2060370337 countsByYear W20603703372022 @default.
• W2060370337 countsByYear W20603703372023 @default.
• W2060370337 crossrefType "journal-article" @default.
• W2060370337 hasAuthorship W2060370337A5012313601 @default.
• W2060370337 hasAuthorship W2060370337A5017472831 @default.
• W2060370337 hasAuthorship W2060370337A5019365851 @default.
• W2060370337 hasAuthorship W2060370337A5030709088 @default.
• W2060370337 hasAuthorship W2060370337A5057655602 @default.
• W2060370337 hasAuthorship W2060370337A5091830603 @default.
• W2060370337 hasBestOaLocation W20603703372 @default.
• W2060370337 hasConcept C104317684 @default.
• W2060370337 hasConcept C112887158 @default.
• W2060370337 hasConcept C165175003 @default.
• W2060370337 hasConcept C174832134 @default.
• W2060370337 hasConcept C178790620 @default.
• W2060370337 hasConcept C185592680 @default.
• W2060370337 hasConcept C2776803919 @default.
• W2060370337 hasConcept C2910768159 @default.
• W2060370337 hasConcept C2993175405 @default.
• W2060370337 hasConcept C32909587 @default.
• W2060370337 hasConcept C547475151 @default.
• W2060370337 hasConcept C55493867 @default.
• W2060370337 hasConcept C71240020 @default.
• W2060370337 hasConceptScore W2060370337C104317684 @default.
• W2060370337 hasConceptScore W2060370337C112887158 @default.
• W2060370337 hasConceptScore W2060370337C165175003 @default.
• W2060370337 hasConceptScore W2060370337C174832134 @default.
• W2060370337 hasConceptScore W2060370337C178790620 @default.

• next