Carrier proteins/systems

In bacteria and plants, the individual enzymes of the fatty acid synthase system are separate, and the acyl radicals are found in combination with a protein called the acyl carrier protein (ACP). However, in yeast, mammals, and birds, the synthase system is a multienzyme polypeptide complex that incorporates ACP, which takes over the role of CoA. It contains the vitamin pantothenic acid in the form of 4 -phosphopan-tetheine (Figure 45-18). The use of one multienzyme functional unit has the advantages of achieving the effect of compartmentalization of the process within the cell without the erection of permeability barriers, and synthesis of all enzymes in the complex is coordinated since it is encoded by a single gene. 

Molecules that cannot pass freely through the lipid bilayer membrane by themselves do so in association with carrier proteins. This involves two processes— facilitated dififrision and active transport—and highly specific transport systems. 

In support of this contention, the carrier protein Aphrodisin makes an early appearance in vaginal secretions. In pre-pubertal hamsters, it thus indicates chemosensory preparation for the onset of female maturity (Magert, 1999). The proven ability of the AOS to modulate the CNS-pituitary-gonadal axis by advancing or retarding endocrine activity (Chap. 5), underlines its role as primarily the chemosensor of the reproductive system. The adaptive consequence of responses, which allows an avoidance of premature breeding, or of a postponement of puberty, would seem to be advantageous. 

Malonyl-CoA Acyl carrier protein transacylase (MCAT or FabD) catalyzes the transfer of a malonyl group between coenzyme A and acyl carrier proteins that are the privileged transporters of the FASH system. Although essential, this enzyme is present in excess and does not have a regulatory role in the FASH pathway, which might explain the relative paucity of reported inhibitors [1],... 

Extracellular ligands (hormones, neurotrophins, carrier protein, adhesion molecules, small molecules, etc.) will bind to specific transmembrane receptors. This binding of specific ligand induces the concentration of the receptor in coated pits and internalization via clathrin-coated vesicles. One of the best studied and characterized examples of RME is the internalization of cholesterol by mammalian cells [69]. In the nervous system, there are a plethora of different membrane receptors that bind extracellular molecules, including neurotrophins, hormones and other cell modulators, being the best studied examples. This type of clathrin-mediated endocytosis is an amazingly efficient process, capable of concentrating... 

A suitable model for the oxygen carrier protein hemerythrin is [Fe2(Et-HPTB)(OBz)](BF4)2 (Et-HPTB = AWAT,iV -tetrakis[(N-ethyl-2-benzimidazolyl)methyl]-2-hydroxy-l,3-diaminopropane, OBz = benzoate). It can mimic the formation of a binuclear peroxo iron complex in the natural system (101). The measured value of -12.8 cm3 mol1 for the activation volume of the oxidation reaction together with the negative value of the activation entropy confirm the highly structured nature of the transition state. 

Once the hapten has been designed and prepared, it is conjugated with a carrier protein to induce the best immunogenicity as possible to elicit an immune response in the animal (most commonly a mouse) in which it is inoculated. The antibodies produced by the defense mechanism of the adaptive immune system that specifically recognizes the hapten are then isolated, overproduced, and purified for testing their catalytic activity toward the targeted chemical reaction. 

Phosphopantetheine tethering is a posttranslational modification that takes place on the active site serine of carrier proteins - acyl carrier proteins (ACPs) and peptidyl carrier proteins (PCPs), also termed thiolation (T) domains - during the biosynthesis of fatty acids (FAs) (use ACPs) (Scheme 23), polyketides (PKs) (use ACPs) (Scheme 24), and nonribosomal peptides (NRPs) (use T domain) (Scheme 25). It is only after the covalent attachment of the 20-A Ppant arm, required for facile transfer of the various building block constituents of the molecules to be formed, that the carrier proteins can interact with the other components of the different multi-modular assembly lines (fatty acid synthases (FASs), polyketide synthases (PKSs), and nonribosomal peptide synthetases (NRPSs)) on which the compounds of interest are assembled. The structural organizations of FASs, PKSs, and NRPSs are analogous and can be divided into three broad classes the types I, II, and III systems. Even though the role of the carrier proteins is the same in all systems, their mode of action differs from one system to another. In the type I systems the carrier proteins usually only interact in cis with domains to which they are physically attached, with the exception of the PPTases and external type II thioesterase (TEII) domains that act in trans. In the type II systems the carrier proteins selectively interact... 

AcpS -like PPTases involved in primary metabolism acting on carrier proteins from FAS systems... 

---