Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.3 (RNase T1)
 1,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently a new family of prolyl isomerases was discovered, which is unrelated with the cyclophilins or the FK-506 binding proteins. Parvulin, the smallest member of this new family, is a protein with only 92 residues, but parvulin-like domains occur in several large proteins that are apparently involved in protein folding or activation processes. We show here that, in addition to its activity in assays with proline-containing tetrapeptides, parvulin catalyzes the proline-limited folding of a variant of ribonuclease T1 with a kcat/Km value of 30,000 M-1 s-1. This value is much smaller than the kcat/Km value of 1.1x10(7) M-1 s-1 determined for the parvulin-catalyzed prolyl isomerization in the tetrapeptide succinyl-Ala-Leu-Pro-Phe-4-nitroanilide. Parvulin itself unfolds and refolds reversibly in a simple two-state reaction with a Gibbs free energy of stabilization of 28 kJ/mol at 10 degrees C. Most of the unfolded parvulin molecules refold in a slow reaction that involves prolyl isomerization and is catalyzed by cyclophilin, another prolyl isomerase. Moreover, parvulin accelerates its own refolding in an autocatalytic fashion, and the rate of refolding increases tenfold when the concentration of parvulin is increased from 0.5 to 3.0 microM. Apparently, small single-domain prolyl isomerases catalyze prolyl isomerization much better in short peptides than in protein folding reactions, presumably because the prolyl bonds are less accessible in refolding protein chains. It is possible that the additional domains of the large prolyl isomerases improve the affinity for protein substrates.
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PMID:Catalysis of protein folding by parvulin. 935 62

Prolyl isomerases accelerate the cis <--> trans isomerization of prolyl peptide bonds during protein folding and probably also in folded proteins. We asked whether this catalytic function is in fact restricted to prolyl bonds or whether the isomerizations of 'normal' non-prolyl peptide bonds are catalyzed as well. By using the P39A variant of ribonuclease T1 as a substrate we find that the trans --> cis isomerization of the Tyr38-Ala39 bond in the refolding of this protein is not catalyzed by prolyl isomerases of the cyclophilin, FKBP and parvulin families. These enzymes are neither able to catalyze amide bond isomerizations in the proline-free model peptide Ala-Ala-Tyr-Ala-Ala.
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PMID:Prolyl isomerases do not catalyze isomerization of non-prolyl peptide bonds. 956 33