Prolyl isomerases parvulins

Prolyl isomerases belong to three structurally diverse families the cyclophilins, the FK506 binding proteins, and the parvulins. Usually, they are abbreviated to Cyp, FKBP and Parv, followed by the molecular mass and, sometimes, an indicator for the subcellular localization. Cypl8cy thus denotes the cytoplasmic cyclophilin with a molecular mass of 18 kDa. This cyclophilin is also often referred to as CypA. 

The prolyl isomerases catalyze isomerizations only at prolyl bonds and not at nonprolyl peptide bonds. The refolding of the P39A variant of RNase Tl, which is limited in rate by the very slow trans —> cis reisomerization of the Tyr38-Ala39 bond (see Section IV.B), is not catalyzed by cyclophilins, FKBPs, or parvulins. These enzymes are also unable to catalyze amide bond isomerizations in the proline-free model peptide Ala-Ala-Tyr-Ala-Ala (Scholz etal., 1998b). 

The periplasm of E. coli contains prolyl isomerases of all three families. PPIA is a member of the cyclophilin family (Liu and Walsh, 1990 Hayano et al., 1991), FkpA or FKBP26 (Horne and Young, 1995) contains a FKBP12-like domain, and SurA (Rouviere and Gross, 1996) and PpiD (Dartigalongue and Raina, 1998) show parvulin domains. SurA is a soluble protein, whereas PpiD is attached to the inner membrane with its catalytic domain exposed to the periplasmic space. 

Behrens and colleagues (2001) investigated SurA both in vivo and in vitro. All regions of this large protein contribute to its function in vivo. Prolyl isomerase activity could be demonstrated for one of the two parvulin domains, but, as in the case of FkpA, this activity seems to be unimportant for SurA function in vivo. SurA has a chaperone function in vitro, which requires the N-terminal part of the protein to be present. 

Rahfeld, J. U., Rucknagel, K. R, Schelbert, B., Ludwig, B., Hacker, J., Mann, K., and Fischer, G. (1994). Confirmation of the existence of a third family among peptidyl prolyl cis-trans isomerases. Amino acid sequence and recombinant production of parvulin. FEBS Lett. 352, 180-184. 

The essential lipoprotein PrsA, which localizes to the outer surface of the cytoplasmic membrane (Figure 7.1), can also be used to enhance secretion of particular proteins [65]. PrsA belongs to the parvulin subfamily of peptidyl-prolyl cis/trans isomerases (PPIases) [66]. The PPIase domain of PrsA exhibits PPIase activity and a possible chaperone activity in vivo at the membrane-cell wall interface [65]. Overexpression of PrsA was shown to enhance the secretion of several extracellular proteins, including a-amylases [57,65]. Furthermore, PrsA overproduction in B. subtilis resulted in 1.5-fold increased secretion and activity of the pharmacologically relevant human interferon-fi (hlNF-fi) with the AmyE propeptide [67]. 

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