2024
Design, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase
Devitt A, Vargas A, Zhu W, Soye B, Butun F, Alt T, Kaley N, Ferreira G, Moran G, Kelleher N, Liu D, Silverman R. Design, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase. ACS Chemical Biology 2024, 19: 1066-1081. PMID: 38630468, PMCID: PMC11274680, DOI: 10.1021/acschembio.4c00022.Peer-Reviewed Original ResearchConceptsActive siteX-ray crystallographyIntact protein mass spectrometryHuman ornithine aminotransferaseNucleophilic additionRing scaffoldMass spectrometryIntermediate speciesProtein mass spectrometryIncreased selectivityTransient state kinetic studiesX-rayMechanistic studiesAdductsSolvent accessibilityKinetic studiesHepatocellular carcinomaProgression of hepatocellular carcinomaMechanism of inactivationStructural evidencePrevalence of hepatocellular carcinomaTreatment of hepatocellular carcinomaCyclohexeneCyclopenteneCrystallography
1976
Inactivation of pyridoxal phosphate dependent enzymes by mono- and polyhaloalanines.
Silverman R, Abeles R. Inactivation of pyridoxal phosphate dependent enzymes by mono- and polyhaloalanines. Biochemistry 1976, 15: 4718-23. PMID: 974085, DOI: 10.1021/bi00666a028.Peer-Reviewed Original ResearchConceptsPyridoxal phosphate dependent enzymesDependent enzymesGamma-elimination reactionActive siteAlanine racemaseGlutamate-pyruvateCovalent modificationMechanism of inactivationEnzymeEnzyme concentrationInactivationCovalent labelingSchiff base formationRate of inactivationPyridoxalGamma-cystathionaseBetaActivated Michael acceptorsBase formationMichael acceptorsMichael addition