Threonine complexes

FIGURE 9.26 The carbohydrate tnoiedes of glycoproteins may be linked to the protein via (a) serine or threonine residues (in the O-linked saccharides) or (b) asparagine residues (in the N-linked saccharides), (c) N-Linked glycoproteins are of three types high mannose, complex, and hybrid, the latter of which combines structures found in the high mannose and complex saccharides. 

Molecules like lactic acid, alanine, and glyceraldehyde are relatively simple because each has only one chirality center and only two stereoisomers. The situation becomes more complex, however, with molecules that have more than one chirality center. As a general rule, a molecule with n chirality centers can have up to 2n stereoisomers (although it may have fewer, as we ll see shortly). Take the amino acid threonine (2-amino-3-hydroxybutanoic acid), for example. Since threonine has two chirality centers (C2 and C3), there are four possible stereoisomers, as shown in Figure 9.10. Check for yourself that the R,S configurations are correct. 

Unique methods based on new principles have been developed within the past 10 years. Threonine (27,28,249) is oxidized by lead tetraacetate or periodic acid to acetaldehyde, which is determined by photometric analysis of its p-hydroxydiphenyl complex or iodometric titration of its combined bisulfite. Serine is oxidized similarly to formaldehyde, which is determined gravimetrically (207) as its dimedon (5,5-dimethyldihydro-resorcinol) derivative or photometric analysis (31) of the complex formed with Eegriwe s reagent (l,8-dihydroxynaphthalene-3,5-disulfonic acid). It appears that the data obtained for threonine and serine in various proteins by these oxidation procedures are reasonably accurate. [Block and Bolling (26) have given data on the threonine and serine content of various proteins. ]... 

The a subunits, for which two isoforms exist in mammals (al, a2), contain conventional protein serine/threonine kinase domains at the N-terminus, with a threonine residue in the activation loop (Thr-172) that must be phosphorylated by upstream kinases (see below) before the kinase is active. The kinase domain is followed by an autoinhibitory domain, whose effect is somehow relieved by interaction with the other subunits. The C-terminal domain of the a subunit is required for the formation of a complex with the C-terminal domain of the (3 subunit, which in turn mediates binding to the y subunit. The al and a2 catalytic subunit isoforms are widely distributed, although a2 is most abundant in muscle and may be absent in cells of the endothelial/hemopoietic lineage. 

Sirolimus (SRL), also termed rapamycin is a macrolide lactone isolated from the ascomycete species Stre-ptomyces hygroscopicus. After binding to its cytosolic receptor FKBP-12 the resulting complex inhibits the multifunctional serine-threonine kinase mTOR (mammalian target of rapamycin). Inhibition of mTOR prevents activation of the p70S6 kinase and successive... 

Tyrosine phosphorylated IRS interacts with and activates PI 3-kinase [3]. Binding takes place via the SRC homology 2 (SH2) domain of the PI 3-kinase regulatory subunit. The resulting complex consisting of INSR, IRS, and PI 3-kinase facilitates interaction of the activated PI 3-kinase catalytic subunit with the phospholipid substrates in the plasma membrane. Generation of PI 3-phosphates in the plasma membrane reemits phospholipid dependent kinases (PDKl and PDK2) which subsequently phosphorylate and activate the serine/threonine kinase Akt (synonym protein... 

Very large Serine/Threonine kinases and the molecular Target of Rapamycin, a naturally occurring secondary metabolite, TOR proteins function within multiprotein complexes to couple cell growth and stress responses to environmental and developmental cues. 

The R2C2 complex has no enTymatic activity, but the binding of cAMP by R dissociates R from C, thereby activating the latter (Figure 43-5). The active C subunit catalyzes the transfet of the y phosphate of ATP to a serine or threonine residue in a variety of proteins. The consensus phosphotylation sites are -Arg-Arg/Lys-X-Ser/Thr- and -Arg-Lys-X-X-Ser-, where X can be any amino acid. 

Figure 52-6. Diagrammatic representation of the structures of the H, A,and B blood group substances. R represents a long complex oligosaccharide chain, joined either to ceramide where the substances are glycosphingolipids, or to the polypeptide backbone of a protein via a serine or threonine residue where the substances are glycoproteins. Note that the blood group substances are biantenna ry ie, they have two arms, formed at a branch point (not indicated) between the GIcNAc—R, and only one arm of the branch is shown. Thus, the H, A,and B substances each contain two of their respective short oligosaccharide chains shown above. The AB substance contains one type A chain and one type B chain.

In mammals and in the majority of bacteria, cobalamin regulates DNA synthesis indirectly through its effect on a step in folate metabolism, catalyzing the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate via two methyl transfer reactions. This cytoplasmic reaction is catalyzed by methionine synthase (5-methyltetrahydrofolate-homocysteine methyl-transferase), which requires methyl cobalamin (MeCbl) (253), one of the two known coenzyme forms of the complex, as its cofactor. 5 -Deoxyadenosyl cobalamin (AdoCbl) (254), the other coenzyme form of cobalamin, occurs within mitochondria. This compound is a cofactor for the enzyme methylmalonyl-CoA mutase, which is responsible for the conversion of T-methylmalonyl CoA to succinyl CoA. This reaction is involved in the metabolism of odd chain fatty acids via propionic acid, as well as amino acids isoleucine, methionine, threonine, and valine. 

Hypermodified nucleosides that contain an attached amino acid at C(6) are important in the biochemistry of RNAs. The Ni11 complex with N-[(9-/3-D-ribofuranozylpurin-6-yl)-carbamoyl]-threonine (699) forms a very stable complex involving N(l) of the purine ring, the amide-N and the carboxylate of the attached threonine as donors.1837... 

A combination of mass spectrometry on purified bands, with limited protein sequence, and generation of antibodies to mucin-specific sequences has established that MUC-1, MUC-2 and MUC-3 are all present in the complex of secreted TES-120 proteins (Loukas et al, 2000). In addition, a further band migrating slightly more slowly than TES-120 represents an as yet unidentified threonine-rich mucin-like gene product. Two further mucins, MUC-4 and MUC-5, have also been cloned (A. Doedens et al., 2000, unpublished results Loukas et al, 2000), but as yet there are no data to suggest that these are secreted by the larvae. In the case of MUC-5, release seems unlikely because it has a relatively high lysine content and it is known that TES-120 does not incorporate lysine (Gems and Maizels, 1996). 

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