Proline, peptide-bound

However, little is currently known about its synthesis. The protein component may be assembled on the ribosomes by the normal mechanism of protein synthesis.324 L-Proline is known to be the precursor of the hydroxy-L-proline found in the glycoprotein,324,325 hydroxylation of the peptide-bound L-proline being catalyzed, in carrot cells, by cytoplasmic enzymes.324... 

The Af-acyl groups in bound proline and hydroxyproline differ from all the other peptide groups in being fully substituted tertiary amides. Whereas secondary peptides (XXXIX) may form anions (XXXX) by abstraction of a proton from the nitrogen atom, the formation of an anion (XXXXII) from a proline peptide (XXXXI) would have to proceed with cleavage of... 

Uitto, J., and Prockop, D. J., 1974, Hydroxylation of peptide-bound proline and lysine before and after chain completion of the polypeptide chains, Arch. Biochem. Biophys. 164 210-217. 

Little is known about the nature of this conversion. Presumably the major amount of hydroxyproline formation occurs when proline is bound in peptide linkage in collagen. This was suggested first by Stetten and Schoenheimer (133). The work of numerous subsequent investigators have supported this (133-136). Mitoma et al. (136) observed a minor degree of incorporation of hydroxyproline into protein in embryonic tissue, but this was overshadowed by the hydroxylation of the peptide-bound proline. 

The biogenesis of the hydroxyproline in collagen has long been under investigation yet the mechanism of its formation and incorporation into protein is still not fully understood. As L-proline- N but not hydroxyproline- N serves as the precursor of the hydroxyproline in collagen (Stetten and Schoenheimer, 1944 Stetten, 1949) it has been postulated that the imino acid may be formed from peptide-bound proline or be derived from an activated rather than a free form of proline. Studies with C-labeled proline and hydroxyproline have confirmed... 

In contrast to the results obtained in animal systems, earher studies suggested that free hydroxyproline may serve as precursor of the hydroxyprohne in actinomycin I (Katz and Goss, 1958, 1959 Katz, Prockop and Udenfriend, 1962). The addition of C-hydroxyproline enhanced formation of actinomycin I suggesting that a direct incorporation of hydroxyprohne could take place (Katz and Goss, 1958, 1959). Isotope dilution experiments have also provided further evidence for this hypothesis (Katz, Prockop and Udenfriend, 1962). In an experiment in which L-proline- C and unlabeled hydroxyproline were supphed to S. antibioticus it was determined that there was a 6-fold dilution of C-label in the hydroxyproline of actinomycin I. Somewhat more direct evidence was obtained with C-hydroxy-L-proline which was incorporated into actinomycin I as peptide-bound hydroxyproline to an appreciable extent (Katz, Prockop and Udenfriend, 1962). The efficiency of incorporation into actinomycin I actually approached that observed in some experiments with L-proline- C. As only a limited amount of C-label was present in the proline (or oxoproline) of actinomycins I, IV and V, it was postulated that free proline is converted to free hydroxyproline which is then incorporated into the antibiotic peptide. If this postulate is true, then the microbial system may differ somewhat from animal... 

L-proline isomer Actinomycin Radioactivity in peptide-bound imino acids ... 

The structurally related myxochromides Aj.j are cyclic hexapeptides produced by several Myxococcus species. These examples contain a proline residue, which is not present in myxochromides Si 3, as the fourth amino acid in their peptide core. The NRPSs responsible for myxochromides A and S biosynthesis have exacdy the same module and domain organization thus, the fourth module of the myxochromide S synthetase must be skipped to account for the natural product. Biochemical experiments revealed that the A domain of this module activates L-proline, but the adjacent PCP domain cannot be phosphopantetheinylated by a PPTase. These results suggest that the C domain of module 5 reacts directly with the tripeptide intermediate bound to the PCP domain of module 3 in myxochromide S biosynthesis. A similar example of domain skipping has been noted in the biosynthesis of the mannopeptimycins. ... 

This enzyme [EC 3.4.11.9] (also known as Xaa-Pro aminopeptidase, X-Pro aminopeptidase, proline amino-peptidase, and aminoacylproline aminopeptidase) catalyzes the hydrolysis of a peptide bond at the iV-terminus of a peptide provided that the iV-terminal amino acyl residue is linked to a prolyl residue by that peptide bond. The enzyme will also act on dipeptides and tripeptides with that same restriction. Either manganese or cobalt is needed as a cofactor. This enzyme appears to be a membrane-bound system in both mammalian and bacterial cells. The protein belongs to the peptidase family M24B. 

The sequence X-P-p-X-P is a consensus sequence for SH3 ligands, in which the two proline residues P are invariant, X is usually an aliphatic residue and p is often a Pro residue. The two invariant proline residues are each bound in a hydrophobic pocket of the SH3 domain. Peptide hgands can be bound in the C- N and also in the N- C direction. Like the SH2 domains, there are many different SH3 domains. The different SH3 domains demonstrate differing binding preferences for Pro-rich sequences, the specificity being determined by the neighboring residues of the invariant proline. 

As mentioned above, the WW domain is another example of a protein-protein interaction module that binds proline-rich sequences (Kay et al., 2000). Dystrophin and utrophin WW domains interact predominantly with the extracellular matrix receptor dystroglycan, which contains a type 1 WW motif of consensus PPxY (reviewed in Ilsley et al., 2002 Winder, 2001). A structure of a WW domain from dystrophin was solved recently as part of a structure including the EF-hand region, and also with and without a bound /3-dystroglycan peptide (Huang et al., 2000). 

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