Prosthetic Groups, Cofactors, and Post-Translational Modifications

Prosthetic Groups, Cofactors, and Post-Translational Modifications 

Frequently, metal ions are associated with the prosthetic group or cofactor. Heme rings usually contain a chelated iron atom. Occasionally, however, these metals are merely bound within folded polypeptide regions with no additional organic constituents required. Many metal ions are known to participate in enzymatic activity. One or more of the ions of Na, K, Ca, Zn, Cu, Mg, Mn, as well as Co and Mo are often required by enzymes to maintain activity. 

Prosthetic groups and cofactors, whether organic or metallic, may be removed from a protein to create an inactive apo protein or enzyme. Loss of these groups may occur through environmental changes, such as removing metal ions from solution or adding denaturants to unfold 

In addition to small organic molecules or metal ions, proteins may have other components tightly associated with them. Nucleoproteins, for instance, contain noncovalently bound DNA or RNA, as in some of the structural proteins of viruses. Lipoproteins contain associated lipids or fatty acids and may also carry cholesterol, as in the high-density and low-density lipoproteins in serum. 

The content by weight of carbohydrate in glycoproteins may vary from only a few percent to over 50 percent in some proteins in mucous secretions. Although the function of the polysaccharide in most glycoproteins is unknown, in some cases it may provide hydrophilicity, recognition, and points of noncovalent interaction with other proteins through lectin-like affinity binding. 

Another form of post-transitional modification that may add carbohydrate to a polypeptide is nonenzymatic glycation. This reaction occurs between the reducing ends of sugar molecules and the amino groups of proteins and peptides. See Section 2.1 for further details and the reaction sequence behind this modification. 

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Many proteins contain carbohydrates and lipids, covalently bound to amino acid side-chains. Others contain covalently bound cofactors and prosthetic groups, such as vitamins and their derivatives, metal ions or haem. Again the attachment of these non-amino acid parts of the protein is part of the process of post-translational modification to form the active protein. 

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