FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W117173627> ?p ?o ?g. }

• W117173627 abstract "Crystals of bovine trypsinogen inhibited with diisopropylfluorophosphate (DFP) were grown at pH 7 and x-ray intensity data to 2.1 A resolution were collected. The reflections were assigned the phases determined by Kossiakoff (1977) for the isomorphous native trypsinogen structure. Using difference fourier techniques, the resulting protein structure was refined to a residual of 18.2%. As expected, a comparison between (DIP)-trypsinogen and the native trypsinogen structures shows all the structural differences to be in the catalytic site region. However, the structure of the catalytic region was expected to be quite similar to that of DFP-inhibited bovine trypsin at neutral pH, but there exist some marked differences. In trypsin, one of the isopropyl groups of the inhibitor is analogous to the leaving group of a specific substrate and is hydrolyzed off the inhibitor. In the resulting monoisopropylphosphoryl (MIP)-trypsin, the inhibitor is oriented with a non-esterified phosphoryl oxygen in the oxyanion stabilization site as expected for a tetrahedral intermediate in proteolysis. His 57 Ne2 points toward the phosphoryl oxygen at the leaving group site, and is in a position suitable for proton donation to the leaving group. By contrast, the inhibitor on DIP-trypsinogen remains intact and the presence of electron density at each of the three possible isopropyl locations indicates that the groups of the inhibitor are less specifically oriented. After independent refinement of each of the three possible orientations, the favored orientation was with isopropyl groups near the oxyanion and leaving group sites and the non-esterified phopsphoryl oxygen hydrogen-bonded through two solvent molecules to Ser 214 O. The imidazole ring of His 57 is displaced from its native position at the catalytic site out into the solvent region where it forms hydrogen-bonds to Tyr 94 0 and through a solvent molecule to Ser 214 O. Ser 195 Oγ has moved closer to the position occupied by the His 57 imidazole in native trypsinogen and MIP-trypsin. Both statistical variation in orientation of the inhibitor and movement of Ser 195 Oγ toward the native imidazole site can be explained by the nonfunctionality of the oxyanion binding site in trypsinogen. The difference between DIP-Tgen and MIP-trypsin thus suggests both non-productive transition state or substrate binding and stereochemical incompatability between the tetrahedral intermediate and the native imidazole site as possible contributors to the relative inactivity of the proenzyme. Conversely, and of more general importance, these results emphasize the importance of exact stereochemical alignment in generating a functional catalytic enzyme." @default.
• W117173627 created "2016-06-24" @default.
• W117173627 creator A5074877796 @default.
• W117173627 date "1982-01-01" @default.
• W117173627 modified "2023-09-27" @default.
• W117173627 title "The Factors Important to Catalysis by Serine Proteases: Structure of Diisopropylfluorophosphate-Inhibited Bovine Trypsinogen Refined at 2.1 Å Resolution" @default.
• W117173627 hasPublicationYear "1982" @default.
• W117173627 type Work @default.
• W117173627 sameAs 117173627 @default.
• W117173627 citedByCount "0" @default.
• W117173627 crossrefType "dissertation" @default.
• W117173627 hasAuthorship W117173627A5074877796 @default.
• W117173627 hasConcept C104264131 @default.
• W117173627 hasConcept C155647269 @default.
• W117173627 hasConcept C179506582 @default.
• W117173627 hasConcept C181199279 @default.
• W117173627 hasConcept C185592680 @default.
• W117173627 hasConcept C206759300 @default.
• W117173627 hasConcept C2778401398 @default.
• W117173627 hasConcept C2780340462 @default.
• W117173627 hasConcept C2781286802 @default.
• W117173627 hasConcept C41183919 @default.
• W117173627 hasConcept C55493867 @default.
• W117173627 hasConcept C71240020 @default.
• W117173627 hasConcept C8010536 @default.
• W117173627 hasConceptScore W117173627C104264131 @default.
• W117173627 hasConceptScore W117173627C155647269 @default.
• W117173627 hasConceptScore W117173627C179506582 @default.
• W117173627 hasConceptScore W117173627C181199279 @default.
• W117173627 hasConceptScore W117173627C185592680 @default.
• W117173627 hasConceptScore W117173627C206759300 @default.
• W117173627 hasConceptScore W117173627C2778401398 @default.
• W117173627 hasConceptScore W117173627C2780340462 @default.
• W117173627 hasConceptScore W117173627C2781286802 @default.
• W117173627 hasConceptScore W117173627C41183919 @default.
• W117173627 hasConceptScore W117173627C55493867 @default.
• W117173627 hasConceptScore W117173627C71240020 @default.
• W117173627 hasConceptScore W117173627C8010536 @default.
• W117173627 hasLocation W1171736271 @default.
• W117173627 hasOpenAccess W117173627 @default.
• W117173627 hasPrimaryLocation W1171736271 @default.
• W117173627 hasRelatedWork W1561690684 @default.
• W117173627 hasRelatedWork W1597564353 @default.
• W117173627 hasRelatedWork W1875979868 @default.
• W117173627 hasRelatedWork W1975616532 @default.
• W117173627 hasRelatedWork W2005532139 @default.
• W117173627 hasRelatedWork W2012931700 @default.
• W117173627 hasRelatedWork W2035938595 @default.
• W117173627 hasRelatedWork W2037850160 @default.
• W117173627 hasRelatedWork W2038073686 @default.
• W117173627 hasRelatedWork W2042201421 @default.
• W117173627 hasRelatedWork W2044740473 @default.
• W117173627 hasRelatedWork W2074308604 @default.
• W117173627 hasRelatedWork W2076568372 @default.
• W117173627 hasRelatedWork W2080048885 @default.
• W117173627 hasRelatedWork W2084974991 @default.
• W117173627 hasRelatedWork W2095245174 @default.
• W117173627 hasRelatedWork W2120827531 @default.
• W117173627 hasRelatedWork W2317210420 @default.
• W117173627 hasRelatedWork W2412418496 @default.
• W117173627 hasRelatedWork W244085261 @default.
• W117173627 isParatext "false" @default.
• W117173627 isRetracted "false" @default.
• W117173627 magId "117173627" @default.
• W117173627 workType "dissertation" @default.