1CSA

THE MUTANT E.COLI F112W CYCLOPHILIN BINDS CYCLOSPORIN A IN NEARLY IDENTICAL CONFORMATION AS HUMAN CYCLOPHILIN

Summary for 1CSA

• Entry DOI: 10.2210/pdb1csa/pdb
• Related: 1BCK 1C5F 1CWA 1CWB 1CWC 1CWF 1CWH 1CWI 1CWJ 1CWK 1CWL 1CWM 1CWO 1CYA 1CYB 1CYN 1IKF 1M63 1MF8 1MIK 1QNG 1QNH 1XQ7 2ESL 2OJU 2POY 2RMA 2RMB 2RMC 2WFJ 2X2C 2X7K 2Z6W 3BO7 3CYS 3EOV
• Related PRD ID: PRD_000142
• Descriptor: CYCLOSPORIN A (1 entity in total)
• Functional Keywords: immunosuppressant, cyclosporin a
• Biological source: TOLYPOCLADIUM INFLATUM
• Total number of polymer chains: 1
• Total formula weight: 1220.63

Authors

Fejzo, J.,Walsh, C.T.,Wagner, G. (deposition date: 1992-02-24, release date: 1994-04-30, Last modification date: 2024-06-05)

Primary citation

Fejzo, J.,Etzkorn, F.A.,Clubb, R.T.,Shi, Y.,Walsh, C.T.,Wagner, G.
The Mutant Escherichia Coli F112W Cyclophilin Binds Cyclosporin a in Nearly Identical Conformation as Human Cyclophilin.
Biochemistry, 33:5711-, 1994

PubMed Abstract: The periplasmic Escherichia coli cyclophilin is distantly related to human cyclophilin (34% sequence identity). Peptidyl-prolyl isomerase activity, cyclosporin A binding, and inhibition of the calcium-dependent phosphatase calcineurin are compared for human and E. coli wild-type and mutant proteins. Like human cyclophilin, the E. coli protein is a cis-trans peptidyl-prolyl isomerase. However, while the human protein binds cyclosporin A tightly (Kd = 17 nM), the E. coli protein does not (Kd = 3.4 microM). The mutant F112W E. coli cyclophilin has enhanced cyclosporin binding (Kd = 170 nM). As for the human protein, the complex of the E. coli mutant with cyclosporin A inhibits calcineurin. Here we describe the structure at pH 6.2 of cyclosporin A bound to the mutant E. coli cyclophilin as solved with solution NMR methods. Despite the low overall sequence identity, the structure of the bound cyclosporin A is virtually identical in both proteins. To assess differences of the cyclosporin binding site, the solution structure of wild-type E. coli cyclophilin was compared with structures of uncomplexed human cyclophilin A and with cyclosporin bound. Despite the structural similarity of bound cyclosporin A, the architecture of the binding site in the E. coli protein is substantially different at the site most distant to tryptophan 121 (human sequence). This site is constructed by a five-residue insertion in a loop of the E. coli protein, replacing another loop in the human protein.

PubMed: 8180197
DOI: 10.1021/BI00185A007

Experimental method

SOLUTION NMR