Substrate specificities of the peptidyl prolyl cis-trans isomerase activities of cyclophilin and FK-506 binding protein: evidence for the existence of a family of distinct enzymes - PubMed (original) (raw)
. 1990 Apr 24;29(16):3813-6.
doi: 10.1021/bi00468a001.
Affiliations
- PMID: 1693856
- DOI: 10.1021/bi00468a001
Substrate specificities of the peptidyl prolyl cis-trans isomerase activities of cyclophilin and FK-506 binding protein: evidence for the existence of a family of distinct enzymes
R K Harrison et al. Biochemistry. 1990.
Abstract
Substrate specificities, as reflected in kc/Km, were determined for the peptidyl prolyl cis-trans isomerase activities of cyclophilin and the FK-506 binding protein (FKBP). The substrates investigated were peptides of the general structure Suc-Ala-Xaa-Pro-Phe-p-nitroanilide, where Xaa = Gly, Ala, Val, Leu, Phe, His, Lys, on Glu. While kc/Km for cyclophilin-catalyzed isomerization shows little dependence on Xaa, kc/Km values for FKBP-catalyzed isomerization display a marked dependence on Xaa and vary over 3 orders of magnitude. An important outcome of this work is the discovery that Suc-Ala-Leu-Pro-Phe-pNA is a reactive substrate for FKBP (kc/Km = 640,000 M-1 s-1). This substrate can be used with FKBP concentrations that are low enough to allow, for the first time, accurate determinations of Ki values for tight-binding inhibitors of FKBP. Using this new assay, we found that FK-506 inhibits FKBP with Ki = 1.7 +/- 0.6 nM. The results of this work support the hypothesis that cyclophilin and FKBP are members of a family of peptidyl prolyl cis-trans isomerases and that the members of this family possess distinct substrate specificities that allow them to play diverse physiologic roles.
Similar articles
- Inhibition of peptidyl-prolyl cis/trans isomerase activity by substrate analog structures: thioxo tetrapeptide-4-nitroanilides.
Schutkowski M, Wöllner S, Fischer G. Schutkowski M, et al. Biochemistry. 1995 Oct 10;34(40):13016-26. doi: 10.1021/bi00040a012. Biochemistry. 1995. PMID: 7548060 - A novel peptidyl-prolyl cis/trans isomerase from Escherichia coli.
Rahfeld JU, Schierhorn A, Mann K, Fischer G. Rahfeld JU, et al. FEBS Lett. 1994 Apr 18;343(1):65-9. doi: 10.1016/0014-5793(94)80608-x. FEBS Lett. 1994. PMID: 8163020 - Mechanistic studies of peptidyl prolyl cis-trans isomerase: evidence for catalysis by distortion.
Harrison RK, Stein RL. Harrison RK, et al. Biochemistry. 1990 Feb 20;29(7):1684-9. doi: 10.1021/bi00459a003. Biochemistry. 1990. PMID: 2184885 - Peptidyl-prolyl cis-trans isomerases, cyclophilin, FK506-binding protein, and ninaA: four of a kind.
Stamnes MA, Zuker CS. Stamnes MA, et al. Curr Opin Cell Biol. 1990 Dec;2(6):1104-7. doi: 10.1016/0955-0674(90)90163-9. Curr Opin Cell Biol. 1990. PMID: 2099804 Review. No abstract available. - Cyclosporin A, FK-506, and rapamycin: pharmacologic probes of lymphocyte signal transduction.
Sigal NH, Dumont FJ. Sigal NH, et al. Annu Rev Immunol. 1992;10:519-60. doi: 10.1146/annurev.iy.10.040192.002511. Annu Rev Immunol. 1992. PMID: 1375473 Review.
Cited by
- A novel multi-functional chloroplast protein: identification of a 40 kDa immunophilin-like protein located in the thylakoid lumen.
Fulgosi H, Vener AV, Altschmied L, Herrmann RG, Andersson B. Fulgosi H, et al. EMBO J. 1998 Mar 16;17(6):1577-87. doi: 10.1093/emboj/17.6.1577. EMBO J. 1998. PMID: 9501079 Free PMC article. - Structure and expression of cytosolic cyclophilin/peptidyl-prolyl cis-trans isomerase of higher plants and production of active tomato cyclophilin in Escherichia coli.
Gasser CS, Gunning DA, Budelier KA, Brown SM. Gasser CS, et al. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9519-23. doi: 10.1073/pnas.87.24.9519. Proc Natl Acad Sci U S A. 1990. PMID: 1702215 Free PMC article. - The immunosuppressive and toxic effects of FK-506 are mechanistically related: pharmacology of a novel antagonist of FK-506 and rapamycin.
Dumont FJ, Staruch MJ, Koprak SL, Siekierka JJ, Lin CS, Harrison R, Sewell T, Kindt VM, Beattie TR, Wyvratt M, et al. Dumont FJ, et al. J Exp Med. 1992 Sep 1;176(3):751-60. doi: 10.1084/jem.176.3.751. J Exp Med. 1992. PMID: 1380976 Free PMC article. - Chaperone domains convert prolyl isomerases into generic catalysts of protein folding.
Jakob RP, Zoldák G, Aumüller T, Schmid FX. Jakob RP, et al. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20282-7. doi: 10.1073/pnas.0909544106. Epub 2009 Nov 17. Proc Natl Acad Sci U S A. 2009. PMID: 19920179 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Medical