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PMID: 1946361 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Crystal structure of recombinant human T-cell cyclophilin A at 2.5 A resolution.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 21 ·1991-11-01 ·Pages 9483-7

Ke HM, Zydowsky LD, Liu J, Walsh CT

Abstract

The structure of the unligated human T-cell recombinant cyclophilin has been determined at 3 A resolution by multipole isomorphous replacement methods and refined at 2.5 A resolution to an R factor of 0.209. The root-mean-square errors of the bond lengths and bond angles are 0.013 A and 2.8 degrees from ideal geometry, respectively. The overall structure is a beta-barrel, consisting of eight antiparallel beta-strands wrapping around the barrel surface and two alpha-helices sitting on the top and the bottom closing the barrel. Inside the barrel, seven aromatic and other hydrophobic residues form a compact hydrophobic core. A loop of Lys-118 to His-126 and four beta-strands (B3-B6) constitute a pocket we speculate to be the binding site of cyclosporin A.

MeSH Terms
Amino Acid Isomerases/chemistry Amino Acid Sequence Binding Sites Carrier Proteins/chemistry Computer Graphics Crystallography Cyclosporine/metabolism Humans Molecular Sequence Data Peptidylprolyl Isomerase Protein Conformation Recombinant Proteins/chemistry Sequence Alignment Solubility X-Ray Diffraction
Chemicals
Carrier Proteins Recombinant Proteins Cyclosporine Amino Acid Isomerases Peptidylprolyl Isomerase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ke H M
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599.
Zydowsky L D
Liu J
Walsh C T
References (32)
32 references, click to expand
  1. The structure of beta-lactoglobulin and its similarity to plasma retinol-binding protein.
    Nature. 1986 Nov 27-Dec 3;324(6095):383-5 PMID: 3785406
  2. Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin.
    Science. 1991 May 10;252(5007):836-9 PMID: 1709301
  3. Orthogonal packing of beta-pleated sheets in proteins.
    Biochemistry. 1982 Aug 17;21(17):3955-65 PMID: 6751382
  4. The anatomy and taxonomy of protein structure.
    Adv Protein Chem. 1981;34:167-339 PMID: 7020376
  5. Cyclophilin: a specific cytosolic binding protein for cyclosporin A.
    Science. 1984 Nov 2;226(4674):544-7 PMID: 6238408
  6. The ninaA gene required for visual transduction in Drosophila encodes a homologue of cyclosporin A-binding protein.
    Nature. 1989 Mar 2;338(6210):67-70 PMID: 2493138
  7. Human and Escherichia coli cyclophilins: sensitivity to inhibition by the immunosuppressant cyclosporin A correlates with a specific tryptophan residue.
    Biochemistry. 1991 Mar 5;30(9):2306-10 PMID: 2001362
  8. Isolation and amino acid sequence of cyclophilin.
    J Biol Chem. 1986 Jun 25;261(18):8547-55 PMID: 3522572
  9. A second cyclophilin-related gene in Saccharomyces cerevisiae.
    Nucleic Acids Res. 1990 Mar 25;18(6):1643 PMID: 2183199
  10. 1H NMR studies on bovine cyclophilin: preliminary structural characterization of this specific cyclosporin A binding protein.
    Biochemistry. 1986 Nov 4;25(22):6778-84 PMID: 3542017
  11. Conformation of polypeptides and proteins.
    Adv Protein Chem. 1968;23:283-438 PMID: 4882249
  12. Resolution of phase ambiguity in macromolecular crystallography.
    Methods Enzymol. 1985;115:90-112 PMID: 4079800
  13. Solution structure of the major binding protein for the immunosuppressant FK506.
    Nature. 1991 May 16;351(6323):248-50 PMID: 2041572
  14. FKB1 encodes a nonessential FK 506-binding protein in Saccharomyces cerevisiae and contains regions suggesting homology to the cyclophilins.
    Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):1029-33 PMID: 1704127
  15. Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant complex.
    Science. 1991 May 10;252(5007):839-42 PMID: 1709302
  16. Yeast cyclophilin: isolation and characterization of the protein, cDNA and gene.
    Gene. 1989 Nov 15;83(1):39-46 PMID: 2687115
  17. Complementary DNA for human T-cell cyclophilin.
    EMBO J. 1987 Apr;6(4):947-50 PMID: 3297675
  18. The molecular structure of insecticyanin from the tobacco hornworm Manduca sexta L. at 2.6 A resolution.
    EMBO J. 1987 Jun;6(6):1565-70 PMID: 3608987
  19. Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin.
    Nature. 1989 Feb 2;337(6206):473-5 PMID: 2644542
  20. Cyclosporin A-binding protein (cyclophilin) of Neurospora crassa. One gene codes for both the cytosolic and mitochondrial forms.
    J Biol Chem. 1988 Oct 5;263(28):14433-40 PMID: 2971658
  21. Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotometric assay.
    Biochemistry. 1991 Jun 25;30(25):6127-34 PMID: 2059621
  22. The three-dimensional structure of P2 myelin protein.
    EMBO J. 1988 Jun;7(6):1597-604 PMID: 2458918
  23. Human cyclophilin B: a second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence.
    Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1903-7 PMID: 2000394
  24. The three-dimensional structure of retinol-binding protein.
    EMBO J. 1984 Jul;3(7):1451-4 PMID: 6540172
  25. Nucleotide sequences of fic and fic-1 genes involved in cell filamentation induced by cyclic AMP in Escherichia coli.
    J Bacteriol. 1989 Aug;171(8):4525-9 PMID: 2546924
  26. Isotope-edited NMR of cyclosporin A bound to cyclophilin: evidence for a trans 9,10 amide bond.
    Science. 1990 Dec 7;250(4986):1406-9 PMID: 2255910
  27. Cloning, expression, and purification of human cyclophilin in Escherichia coli and assessment of the catalytic role of cysteines by site-directed mutagenesis.
    Proc Natl Acad Sci U S A. 1990 Mar;87(6):2304-8 PMID: 2179953
  28. Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins.
    Nature. 1989 Feb 2;337(6206):476-8 PMID: 2492638
  29. The NMR structure of cyclosporin A bound to cyclophilin in aqueous solution.
    Biochemistry. 1991 Jul 2;30(26):6563-74 PMID: 2054355
  30. Crystallographic R factor refinement by molecular dynamics.
    Science. 1987 Jan 23;235(4787):458-60 PMID: 17810339
  31. Drosophila ninaA gene encodes an eye-specific cyclophilin (cyclosporine A binding protein).
    Proc Natl Acad Sci U S A. 1989 Jul;86(14):5390-4 PMID: 2664782
  32. NMR studies of [U-13C]cyclosporin A bound to cyclophilin: bound conformation and portions of cyclosporin involved in binding.
    Biochemistry. 1991 Jul 2;30(26):6574-83 PMID: 2054356
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.21.9483
Published
1991-11-01
Pages
9483-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC52742
Subset
IM
Grants
NIEHS NIH HHS · ES05459 · United States
NIGMS NIH HHS · GM06920 · United States
NIGMS NIH HHS · GM20011 · United States
Databases
PDB
UNKNOWN
External Links
PubMed source DOI: 10.1073/pnas.88.21.9483 PMC Full Text View journal details
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