FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2023722477> ?p ?o ?g. }

• W2023722477 endingPage "340" @default.
• W2023722477 startingPage "321" @default.
• W2023722477 abstract "The structure of the HIV-1 protease in complex with a pseudo-C2 symmetric inhibitor, which contains a central difluoroketone motif, has been determined with X-ray diffraction data extending to 1.7 A resolution. The electron density map clearly indicates that the inhibitor is bound in a symmetric fashion as the hydrated, or gemdiol, form of the difluoroketone. Refinement of the complex reveals a unique, and almost symmetric, set of interactions between the geminal hydroxyl groups, the geminal fluorine atoms, and the active-site aspartate residues. Several hydrogen bonding patterns are consistent with that conformation. The lowest energy hydrogen disposition, as determined by semiempirical energy calculations, shows only one active site aspartate protonated. A comparison between the corresponding dihedral angles of the difluorodiol core and those of a hydrated peptide bond analog, calculated ab-initio, shows that the inhibitor core is a mimic of a hydrated peptide bond in a gauche conformation. The feasibility of an anti-gauche transition for a peptide bond after hydration is verified by extensive molecular dynamics simulations. The simulations suggest that rotation about the C-N scissile bond would readily occur after hydration and would be driven by the optimization of the interactions of peptide side-chains with the enzyme. These results, together with the characterization of a transition state leading to bond breakage via a concerted exchange of two protons, suggest a proteolysis mechanism whereby only one active site aspartate is initially protonated. The steps of this mechanism are: asymmetric binding of the substrate; hydration of the peptidic carbonyl by an active site water; proton translocation between the active site aspartate residues simultaneously with carbonyl hydration; optimization of the binding of the entire substrate facilitated by the flexible structure of the hydrated peptide bond, which, in turn, forces the hydrated peptide bond to assume a gauche conformation; simultaneous proton exchange whereby one hydroxyl donates a proton to the charged aspartate, and, at the same time, the nitrogen lone pair accepts a proton from the other aspartate; and, bond breakage and regeneration of the initial protonation state of the aspartate residues." @default.
• W2023722477 created "2016-06-24" @default.
• W2023722477 creator A5037802350 @default.
• W2023722477 creator A5064632351 @default.
• W2023722477 creator A5069426753 @default.
• W2023722477 creator A5079612043 @default.
• W2023722477 date "1996-01-01" @default.
• W2023722477 modified "2023-09-27" @default.
• W2023722477 title "Inhibition and catalytic mechanism of HIV-1 aspartic protease" @default.
• W2023722477 cites W1571253423 @default.
• W2023722477 cites W1963513750 @default.
• W2023722477 cites W1973485456 @default.
• W2023722477 cites W1979853120 @default.
• W2023722477 cites W1985535752 @default.
• W2023722477 cites W1985948047 @default.
• W2023722477 cites W2003844316 @default.
• W2023722477 cites W2011805684 @default.
• W2023722477 cites W2028414025 @default.
• W2023722477 cites W2030402747 @default.
• W2023722477 cites W2032713338 @default.
• W2023722477 cites W2035286938 @default.
• W2023722477 cites W2038169951 @default.
• W2023722477 cites W2039035988 @default.
• W2023722477 cites W2041299378 @default.
• W2023722477 cites W2041578795 @default.
• W2023722477 cites W2048188367 @default.
• W2023722477 cites W2058155604 @default.
• W2023722477 cites W2063713316 @default.
• W2023722477 cites W2071834037 @default.
• W2023722477 cites W2083547109 @default.
• W2023722477 cites W2086064699 @default.
• W2023722477 cites W2090920284 @default.
• W2023722477 cites W2106484175 @default.
• W2023722477 cites W2123166384 @default.
• W2023722477 cites W2126996034 @default.
• W2023722477 cites W2141385111 @default.
• W2023722477 cites W2157809663 @default.
• W2023722477 cites W2162166182 @default.
• W2023722477 doi "https://doi.org/10.1006/jmbi.1996.0026" @default.
• W2023722477 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8551523" @default.
• W2023722477 hasPublicationYear "1996" @default.
• W2023722477 type Work @default.
• W2023722477 sameAs 2023722477 @default.
• W2023722477 citedByCount "168" @default.
• W2023722477 countsByYear W20237224772012 @default.
• W2023722477 countsByYear W20237224772013 @default.
• W2023722477 countsByYear W20237224772014 @default.
• W2023722477 countsByYear W20237224772015 @default.
• W2023722477 countsByYear W20237224772016 @default.
• W2023722477 countsByYear W20237224772017 @default.
• W2023722477 countsByYear W20237224772018 @default.
• W2023722477 countsByYear W20237224772019 @default.
• W2023722477 countsByYear W20237224772020 @default.
• W2023722477 countsByYear W20237224772021 @default.
• W2023722477 countsByYear W20237224772022 @default.
• W2023722477 countsByYear W20237224772023 @default.
• W2023722477 crossrefType "journal-article" @default.
• W2023722477 hasAuthorship W2023722477A5037802350 @default.
• W2023722477 hasAuthorship W2023722477A5064632351 @default.
• W2023722477 hasAuthorship W2023722477A5069426753 @default.
• W2023722477 hasAuthorship W2023722477A5079612043 @default.
• W2023722477 hasConcept C112887158 @default.
• W2023722477 hasConcept C145148216 @default.
• W2023722477 hasConcept C147597530 @default.
• W2023722477 hasConcept C161790260 @default.
• W2023722477 hasConcept C178790620 @default.
• W2023722477 hasConcept C181199279 @default.
• W2023722477 hasConcept C185592680 @default.
• W2023722477 hasConcept C2776714187 @default.
• W2023722477 hasConcept C2777583353 @default.
• W2023722477 hasConcept C2779281246 @default.
• W2023722477 hasConcept C2779758233 @default.
• W2023722477 hasConcept C29135686 @default.
• W2023722477 hasConcept C30095370 @default.
• W2023722477 hasConcept C31684184 @default.
• W2023722477 hasConcept C32909587 @default.
• W2023722477 hasConcept C41183919 @default.
• W2023722477 hasConcept C55493867 @default.
• W2023722477 hasConcept C71240020 @default.
• W2023722477 hasConcept C8010536 @default.
• W2023722477 hasConcept C87282627 @default.
• W2023722477 hasConceptScore W2023722477C112887158 @default.
• W2023722477 hasConceptScore W2023722477C145148216 @default.
• W2023722477 hasConceptScore W2023722477C147597530 @default.
• W2023722477 hasConceptScore W2023722477C161790260 @default.
• W2023722477 hasConceptScore W2023722477C178790620 @default.
• W2023722477 hasConceptScore W2023722477C181199279 @default.
• W2023722477 hasConceptScore W2023722477C185592680 @default.
• W2023722477 hasConceptScore W2023722477C2776714187 @default.
• W2023722477 hasConceptScore W2023722477C2777583353 @default.
• W2023722477 hasConceptScore W2023722477C2779281246 @default.
• W2023722477 hasConceptScore W2023722477C2779758233 @default.
• W2023722477 hasConceptScore W2023722477C29135686 @default.
• W2023722477 hasConceptScore W2023722477C30095370 @default.
• W2023722477 hasConceptScore W2023722477C31684184 @default.
• W2023722477 hasConceptScore W2023722477C32909587 @default.
• W2023722477 hasConceptScore W2023722477C41183919 @default.
• W2023722477 hasConceptScore W2023722477C55493867 @default.

• next