Solvent content of protein crystals.

Publisher Summary This chapter deals with the recent developments regarding the description and nature of the conformation of proteins and polypeptides with special reference to the stereochemical aspects of the problem. This chapter considers the parameters that are required for an adequate description of a polypeptide chain. This chapter focuses the attention on what may be called “internal parameters”—that is, those which can be defined in terms of the relationships among atoms or units that form the building blocks of the polypeptide chains. This chapter also provides an account of the mathematical method of utilizing these parameters for calculating the coordinates of all the atoms in a suitable frame of reference, so that all the interatomic distances, and bond angles, can be calculated and their consequences worked out. This chapter observes conformations in amino acids, peptides, polypeptides, and proteins.

Conformation of Polypeptides and Proteins

Determination of the secondary structures of proteins by circular dichroism and optical rotatory dispersion.

Electrostatic Basis for Enzyme Catalysis

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.

Role of a Buried Acid Group in the Mechanism of Action of 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 A resolution and interpreted in terms of a previously reported sequence of 241 amino-acids. The map has been derived from a Fourier synthesis of 24,500 terms and represents two crystallographically independent molecules, each of molecular weight 25,000, which are nearly identical in their tertiary structure. The enzyme is composed almost entirely of extended polypeptide chains. A chemical marker unambiguously defines the position of the active centre. The position and orientation of the residues known to be important in catalysis are clearly seen. The mechanism by which the inactive precursor is converted into an active enzyme is revealed.

P.B. Sigler

Papers

Three-dimensional Structure of Tosyl-α-chymotrypsin

Structure of crystalline α-chymotrypsin

An X-ray diffraction study of inhibited derivatives of α-chymotrypsin

A displacement reaction between a polynucleotide Helix and a random coil.

A means of promoting heavy-atom binding in protein crystals.