Role of a Buried Acid Group in the Mechanism of Action of Chymotrypsin

@article{Blow1969RoleOA,
  title={Role of a Buried Acid Group in the Mechanism of Action of Chymotrypsin},
  author={David M. Blow and Jens J. Birktoft and Brian S. Hartley},
  journal={Nature},
  year={1969},
  volume={221},
  pages={337-340}
}
The catalytic site of chymotrypsin contains an interior aspartic acid hydrogen-bonded to a histidine which in its turn is hydrogen-bonded to a serine. Polarization of the system due to the buried negative charge of the aspartic acid residue would make the serine oxygen strongly nucleophilic and would explain its reactivity towards amides and esters. 
A low-barrier hydrogen bond in the catalytic triad of serine proteases.
TLDR
Spectroscopic properties of chymotrypsin and model compounds indicate that a low-barrier hydrogen bond participates in the mechanism of serine protease action, supported by the chemical shift of this proton, the deuterium isotope effect on thechemical shift, and the properties of hydrogen-bonded model compounds in organic solvents.
Chymotrypsin: molecular and catalytic properties.
  • W. Appel
  • Biology, Chemistry
    Clinical biochemistry
  • 1986
Electrostatic effect on catalytic rate enhancement in serine proteinases
The hypothesis that an electrostatic effect of the buried aspartate side chain may contribute considerably to the extreme catalytic power of serine proteinases is presented. This statement is based
HIGH RESOLUTION NMR STUDY OF THE CHARGE RELAY SYSTEM IN CHYMOTRYPSIN
TLDR
This investigation was to determine whether there are preformed hydrogen bonds at the active site of chymotrypsin, and if so, to see how they are involved in the charge relay system.
Unusually large electrostatic field effect of the buried aspartate in serine proteinases: Source of catalytic power
Calculating the electrostatic potential around the Ser–His–Asp catalytic triad in serine proteinases the very important substituent effect of the buried aspartate is revealed. It is found that the
Effects of neutralization of amino groups on the kinetics of chymotrypsin.
  • B. Hofstee
  • Biology
    Biochemical and biophysical research communications
  • 1970
Properties of the active center histidine of -chymotrypsin.
...
...

References

SHOWING 1-10 OF 22 REFERENCES
Structure of Chymotrypsinogen B compared with Chymotrypsinogen A and Trypsinogen
Comparison of the amino-acid sequences of the three proteins shows that a common pattern of invariant non-polar residues exists. This permits a tentative assignment of exterior and interior
Three-dimensional Structure of Tosyl-α-chymotrypsin
A model is proposed for the structure of an inhibited derivative of an enzyme which hydrolyses proteins. It is based on a map of the electron density distribution at 2 Å resolution and interpreted in
Corrections to the amino acid sequence of bovine chymotrypsinogen A.
Reinvestigation of the amino acid sequence of bovine chymotrypsinogen A suggests that the amino acid sequence at the N-terminus of the B-chain (residues 16-19) is -Ile-Val-Asn-Gly- rather than
The binding of inhibitors to α-chymotrypsin
TLDR
The binding of the uncharged amide inhibitor is independent of pH over the range investigated, and the significance of the binding constants with respect to the enzymic catalysis is discussed.
ON THE STRUCTURE AND FUNCTION OF BOVINE TRYPSINOGEN AND TRYPSIN.
TLDR
Examination of this preliminary structure of bovine trypsinogen suggests certain tentative conclusions concerning the relationship between the structure and the function of the protein.
Proton Transfer, Acid-Base Catalysis, and Enzymatic Hydrolysis. Part I: ELEMENTARY PROCESSES†‡
The proton occupies a special position as a promoter and mediator in chemical reactions occurring in solution. Many reactions in organic chemistry are catalysed by acids or bases; likewise, most
Electrophoretic Mobilities of Peptides on Paper and their Use in the Determination of Amide Groups
TLDR
Electrophoretic Mobilities of Peptides on Paper and their Use in the Determination of Amide Groups and their use in the determination of amide groups are studied.
...
...