Postranslational modifications

Small methyl groups are important in the stractnre of some small compounds, nucleotides, some bases in DNA mole-cnles and in postranslational modification of amino acids in proteins. The transfer of a single carbon atom is important in the synthesis of purine nncleotides. The componnds involved in the whole process of methyl gronp transfer, and are carbon metolism, are methionine, homocysteine, serine and the vitamins, folic acid and B12. 

Recent studies have shown that the acetylation or deacetylation of the histones of the nucleosome plays an important role in the regulation of transcriptional activity. Acetylation of the histones (review Hassig and Schreiber, 1997) is a postranslational modification which is usually performed on lysine residues at the N-terminus and requires specific enzymes,the histone acetyl transferases (HATs). Removal of the acetyl group also requires specific enzymes, the histone deacetylases (HDAC). Most importantly, the acetylation of histones is accompanied by a loss of postive charges which is thought to have a profound influence on the nucleosome structure and on the strength of DNA-binding. 

I [al(l)]2a2 ct 1(1)3 Bone, Tendon, Skin, Dentin, Fascia, Arteries Osteogensis Imperfacta (01) and Ehlers-Danlos Syndrome (EDS). Both syndromes are clinically heterogeneous due to genetic defects that affect the biosynthesis, assembly, postranslational modification, secretion, fibrillogenesis, or other extracellular matrix components. 

The mechanisms involved in the induction of various pathologies by a-syn are not well understood, but a-syn oligomerization and its other postranslational modifications are suggested to play an important role. 

Other covalent modifications These may be required for the functional activity of a protein. For example, additional carboxyl groups can be added to glutamate residues by vitamin Independent carboxylation (see p. 387). The resulting y-carboxy-glutamate resides are esssential for the activity of several of the blood-clotting proteins. Attachment of lipids, such as farnesyl groups, can help anchor proteins in membranes. In addition, many proteins are acetylated postranslationally. 

Finally, 1964 saw the publication of a discovery whose impact resonated only in 1996, but quite emphatically the observation by V. Allfrey, and A. E. Mirsky that histone proteins are subjected to postranslational covalent modification via the acetylation and methylation of lysine residues in their NH2-terminal tails (Sections IV.A and IV.C). Because the modifications reduce the positive charge of the histones (and thus have the potential to alter the way histones interact with DNA), it was immediately suspected they might have regulatory consequences. Conclusive evidence to that effect was obtained in 1998 (Section IV.C). 

---