Prolyl peptides

Conversions of peptide-prolyl and peptide-lysyl residues to hydroxyprolyl and hydroxylsyl residues are accomplished by iron-dependent enzymes utilizing... 

Pollock SB, Kent SB (2011) An investigation into the origin of the dramatically reduced reactivity of peptide-prolyl-thioesters in native chemical ligation. Chem Commun 47 2342-2344... 

Furthermore, D- and L-prolyl-(l,l-dimefhyl)-l,2-diaminoethyl (Pro-DADME) segments have been used successfully to connect two y9-peptide strands via their C-termini and to promote the formation of a parallel hairpin (e.g. 123) in both solution (CD3OH) and solid state (Fig. 2.32) [196]. 

Other interesting examples of proteases that exhibit promiscuous behavior are proline dipeptidase from Alteromonas sp. JD6.5, whose original activity is to cleave a dipeptide bond with a prolyl residue at the carboxy terminus [121, 122] and aminopeptidase P (AMPP) from E. coli, which is a prohne-specific peptidase that catalyzes the hydrolysis of N-terminal peptide bonds containing a proline residue [123, 124]. Both enzymes exhibit phosphotriesterase activity. This means that they are capable of catalyzing the reaction that does not exist in nature. It is of particular importance, since they can hydrolyze unnatural substrates - triesters of phosphoric acid and diesters of phosphonic acids - such as organophosphorus pesticides or organophosphoms warfare agents (Scheme 5.25) [125]. 

Figure 5-9. Isomerization of the N-a, prolyl peptide bond from a cis to a trans configuration relative to the backbone of the polypeptide.

Figure 28-11. The prolyl hydroxylase reaction. The substrate is a proline-rich peptide. During the course of the reaction, molecular oxygen is incorporated into both succinate and proline. Lysyl hydroxylase catalyzes an analogous reaction.

F. Marcus, Preferential Cleavage at Aspartyl-Prolyl Peptide Bonds in Dilute Acid , Int. J. Pept. Protein Res. 1985, 25, 542-546. 

In native collagen, all Gly-Pro and Xaa-Hyp peptide bonds are in the trans conformation, whereas in the unfolded state, a significant fraction of cis isomers populates at each Gly-Pro and Xaa-Hyp peptide bond, cis-to-trans isomerization reactions at prolyl peptide bonds are the origin for the observed slow kinetics of triple helix formation" as shown by their high activation energy ( 72 kj moG )" and their acceleration by prolyl... 

Prolyl endopeptidase (PEP, EC 3.4.21.26) is the only serine protease which is known to cleave a peptide substrate in the C terminal side of a proline residue... 

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. 

This enzyme [EC 3.4.14.1], also called cathepsin C and cathepsin J, catalyzes the hydrolysis of a peptide bond resulting in the release of an N-terminal dipeptide, XaaXbb-Xcc, except when Xaa is an arginyl or a lysyl residue, or Xbb or Xcc is a prolyl residue. This enzyme, a member of the peptidase family Cl, is a CF-dependent lysosomal cysteine-type peptidase. 

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