The structure of the classical acute phase reactant human C-reactive protein provides evidence that phosphocholine binding is mediated through calcium and a hydrophobic pocket centred on Phe 66. The residue Glu 81 is suitably positioned to interact with the choline group. A cleft on the pentameric face opposite to that containing the calcium site may have an important functional role. The structure provides insights into the molecular mechanisms by which this highly conserved plasma protein, for which no polymorphism or deficiency state is known, may exert its biological role.

The serpins are a widely distributed family of proteins with diverse functions; they include the key serine protease inhibitors of human plasma as well as noninhibitory homologues such as hormone-binding globulins, angiotensinogen and egg-white ovalbumin. Sequence alignment based on the crystal structure. On the cleaved form of the archetypal serpin, alpha 1-antitrypsin, indicates that the serpins share a common highly ordered structure. On cleavage of the reactive centre peptide bond, they characteristically undergo a remarkable conformational change, the newly generated C terminus moving some 70 A to the opposite pole of the molecule. The structure of this post-cleavage form is known, but the conformation of the intact serpins and in particular that of their reactive centre is not. Wright et al.'s structure of plakalbumin (ovalbumin cleaved by subtilisin) has provided evidence for the conformational change that results from cleavage. We have now determined the structure of native ovalbumin to 1.95 A resolution and have found that the intact peptide loop forming the analogue to the reactive centre of the inhibitory serpins takes the unexpected form of a protruding, isolated helix. This model of the intact structures of the serpins suggests how they may interact with their target proteases.

No abstract