Identification of Solvent-exposed Regions of an FK-506 Analog, Ascomycin, Bound to FKBP Using a Paramagnetic Probe

Overview

Journal J Biomol NMR

Publisher Springer

Specialties Molecular Biology
Nuclear Medicine

Date 1992 Jan 1

PMID 1384850

Citations 5

Authors

A M Petros

P Neri

S W Fesik

Affiliations

Soon will be listed here.

Abstract

The solvent-exposed regions of (U-13C)ascomycin when bound to its putative target protein, FKBP, have been identified based on the different proton longitudinal relaxation rates (R1 = 1/T1) measured in the absence and presence of the paramagnetic relaxation reagent, 4-hydroxy-2,2,6,6-tetramethyl-piperidinyl-1-oxy (HyTEMPO). The proton T1S of bound ascomycin were determined using a pulse sequence (T1-HMQC) which consists of a 180 degree proton pulse and a variable delay (tau) followed by a heteronuclear multiple quantum correlation (HMQC) experiment. The solvent-exposed regions of ascomycin determined by these experiments are compared to NOE data in which ascomycin/FKBP contacts were identified and to the X-ray structure of the FK-506/FKBP complex.

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References

Siekierka J, Hung S, Poe M, Lin C, Sigal N . A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin. Nature. 1989; 341(6244):755-7. DOI: 10.1038/341755a0. View

Hatanaka H, Kino T, Miyata S, Inamura N, Kuroda A, Goto T . FR-900520 and FR-900523, novel immunosuppressants isolated from a Streptomyces. II. Fermentation, isolation and physico-chemical and biological characteristics. J Antibiot (Tokyo). 1988; 41(11):1592-601. DOI: 10.7164/antibiotics.41.1592. View

Petros A, Mueller L, Kopple K . NMR identification of protein surfaces using paramagnetic probes. Biochemistry. 1990; 29(43):10041-8. DOI: 10.1021/bi00495a005. View

Standaert R, Galat A, Verdine G, Schreiber S . Molecular cloning and overexpression of the human FK506-binding protein FKBP. Nature. 1990; 346(6285):671-4. DOI: 10.1038/346671a0. View

Van Duyne G, Standaert R, Karplus P, Schreiber S, Clardy J . Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant complex. Science. 1991; 252(5007):839-42. DOI: 10.1126/science.1709302. View