Covalent Linkage: II. Intramolecular Linkages

  • Rosa Uy
  • Finn Wold


In this section on immobilized enzymes a consideration of covalent intramolecular linkages may appear somewhat irrelevant in that very little, if any, immobilization can be achieved by intramolecular cross-linking reactions. However, since most of the techniques and reagents used for intermolecular cross-link formation are the same as those used to form intramolecular bonds, it is safe to conclude that intramolecular linkages are natural side reactions of many of the immobilization reactions. This, in turn, means that in assessing the properties of an immobilized enzyme, one needs to consider the effects of intramolecular cross-links as well as the effects of the immobilization, and such considerations should therefore justify the inclusion of this chapter. A brief review of nature’s own intramolecular protein cross-links should provide convincing evidence that the cross-link effects indeed can be quite substantial. The most obvious natural cross-link is the disulfide bond, which in most globular proteins imparts unique permanence to the proper three-dimensional folded structure. Especially in cases where the native molecule is composed of multiple polypeptide chains linked by interchain disulfide bonds is the cross-link an essential feature of the structural integrity of the molecule. In the case of some of the structural proteins, multiple disulfide bonds contribute structural rigidity and inertness to the molecular complexes. Similarly, in the case of the very stable and metabolically inert proteins of connective tissue, collagen and elastin, a whole group of unique cross-links derived from oxidatively deaminated lysines and hydroxylysines contribute to the structural properties and undoubtedly also to the metabolic intractability of these proteins. In the formation of the final product of the blood-clotting cascade, the fibrin network is cross-linked by intra- and intermolecular amide bonds between lysine -amino groups and glutamic acid γ-carboxyl groups through the action of the enzyme transglutaminase (factor XIII in the series of plasma clotting factors). Again the role of the cross-links appears to be to fix and stabilize specific molecular conformations and associations. Since the transglutaminase enzyme now has been found to be present in other tissues as well as in the plasma, it seems reasonable to conclude that this cross-linking reaction must be important to processes other than just coagulation.


Covalent Linkage Subunit Structure FEBS Letter Glycerol Kinase Hexamethylene Diisocyanate 
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Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Rosa Uy
    • 1
  • Finn Wold
    • 1
  1. 1.Department of BiochemistryUniversity of MinnesotaSt. PaulUSA

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