DOI: 10.1021/bi962013o. A New Concept for the Mechanism of Action of Chymotrypsin: The Role of the Low-Barrier Hydrogen Bond

A New Concept for the Mechanism of Action of Chymotrypsin: The Role of the Low-Barrier Hydrogen Bond

10.1021/bi962013o

Crossref journal-article

American Chemical Society (ACS)

Biochemistry (316)

Bibliography

Cassidy, C. S., Lin, J., & Frey, P. A. (1997). A New Concept for the Mechanism of Action of Chymotrypsin:â The Role of the Low-Barrier Hydrogen Bond. Biochemistry, 36(15), 4576â4584.

Authors 3

Constance S. Cassidy (first)
Jing Lin (additional)
Perry A. Frey (additional)

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Other analogs are DIP-Cht, MIP-Cht, phenylsulfonyl-Cht, and peptidylboronyl-Cht. The limitations of these as structural analogs of tetrahedral intermediates include the absence of anionic oxygen in the DIP, phenylsulfonyl, and peptidylboronyl groups; the delocalization of negative charge over two oxygens in the MIP group; the localization of a negative charge on boron in the peptidylboronyl groups; and the absence of substituents to occupy the S1and S2specificity binding sites of Cht in DIP and MIP. Peptide aldehydes form tetrahedral adducts with Ser 195, but the hemiacetal oxyanion does not occupy the oxyanion binding site. It is instead rotated into the leaving group position and forms an intimate ion pair with Nε2of His 57 (James et al., 1980; Delbaere & Brayer, 1985; Kurinov & Harrison, 1996).
Preliminary data from one experiment on the complex of chymotrypsin withN-AcVF-CF3indicate a pKaof approximately 12 for the H57−D102 diad based on observation of the LBHB proton, which appears at 18.8 ppm. The LBHB formed byN-AcVF-CF3appears similar to that fromN-AcLF-CF3, in conformance with inhibitory potency and the reactivity of the corresponding substrate (Brady & Abeles, 1990).
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Dates

Type	When
Created	23 years ago (July 26, 2002, 1:05 a.m.)
Deposited	3 years, 10 months ago (Sept. 22, 2021, 8:20 p.m.)
Indexed	3 weeks, 2 days ago (July 28, 2025, 5:43 p.m.)
Issued	28 years, 4 months ago (April 1, 1997)
Published	28 years, 4 months ago (April 1, 1997)
Published Online	28 years, 4 months ago (April 15, 1997)
Published Print	28 years, 4 months ago (April 1, 1997)

Funders 0

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BibTeX

@article{Cassidy_1997, title={A New Concept for the Mechanism of Action of Chymotrypsin: The Role of the Low-Barrier Hydrogen Bond}, volume={36}, ISSN={1520-4995}, url={http://dx.doi.org/10.1021/bi962013o}, DOI={10.1021/bi962013o}, number={15}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={Cassidy, Constance S. and Lin, Jing and Frey, Perry A.}, year={1997}, month=apr, pages={4576–4584} }

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    },
    {
      "key": "atypb89/atypb90",
      "volume-title": "Biochemistry 33, 7326\u22127336",
      "author": "Yennawar N. H.",
      "year": "1994"
    },
    {
      "key": "atypb91/atypb92",
      "doi-asserted-by": "crossref",
      "DOI": "10.1021/ja00132a002",
      "volume": "117",
      "author": "Zhong S.",
      "year": "1995",
      "journal-title": "J. Am. Chem. Soc."
    },
    {
      "key": "bi962013ob00001/bi962013ob00001_1",
      "volume-title": "nuclear magnetic resonance",
      "author": "Abbreviations NMR"
    },
    {
      "key": "bi962013ob00002/bi962013ob00002_1",
      "unstructured": "Other analogs are DIP-Cht, MIP-Cht, phenylsulfonyl-Cht, and peptidylboronyl-Cht. The limitations of these as structural analogs of tetrahedral intermediates include the absence of anionic oxygen in the DIP, phenylsulfonyl, and peptidylboronyl groups; the delocalization of negative charge over two oxygens in the MIP group; the localization of a negative charge on boron in the peptidylboronyl groups; and the absence of substituents to occupy the S1and S2specificity binding sites of Cht in DIP and MIP. Peptide aldehydes form tetrahedral adducts with Ser 195, but the hemiacetal oxyanion does not occupy the oxyanion binding site. It is instead rotated into the leaving group position and forms an intimate ion pair with N\u03b52of His 57 (James et al., 1980; Delbaere & Brayer, 1985; Kurinov & Harrison, 1996)."
    },
    {
      "key": "bi962013ob00003/bi962013ob00003_1",
      "unstructured": "Preliminary data from one experiment on the complex of chymotrypsin withN-AcVF-CF3indicate a pKaof approximately 12 for the H57\u2212D102 diad based on observation of the LBHB proton, which appears at 18.8 ppm. The LBHB formed byN-AcVF-CF3appears similar to that fromN-AcLF-CF3, in conformance with inhibitory potency and the reactivity of the corresponding substrate (Brady & Abeles, 1990)."
    },
    {
      "key": "bi962013ob00004/bi962013ob00004_1",
      "volume-title": "Westler measured the fractionation factor for the low-field proton in the protonated triad of chymotrypsinogen and found it to be 0.4 (Markley & Westler",
      "author": "Markley M.",
      "year": "1996"
    },
    {
      "key": "bi962013ob00006/bi962013ob00006_1",
      "volume-title": "the main chain hydrogen bonds from glycine 193 and Ser 195 stabilize the oxyanion, and the resulting electrostatic interaction with His 57 keeps it protonated (Henderson",
      "author": "In",
      "year": "1970"
    }
  ],
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    "1520-4995"
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  "container-title-short": "Biochemistry",
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