1AUI

HUMAN CALCINEURIN HETERODIMER

Summary for 1AUI

• Entry DOI: 10.2210/pdb1aui/pdb
• Descriptor: SERINE/THREONINE PHOSPHATASE 2B, ZINC ION, FE (III) ION, ... (6 entities in total)
• Functional Keywords: hydrolase, phosphatase, immunosuppression
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus (By similarity): Q08209
• Total number of polymer chains: 2
• Total formula weight: 78229.95

Authors

Kissinger, C.R.,Parge, H.E.,Knighton, D.R.,Pelletier, L.A.,Lewis, C.T.,Tempczyk, A.,Villafranca, J.E. (deposition date: 1997-08-27, release date: 1997-12-03, Last modification date: 2024-02-07)

Primary citation

Kissinger, C.R.,Parge, H.E.,Knighton, D.R.,Lewis, C.T.,Pelletier, L.A.,Tempczyk, A.,Kalish, V.J.,Tucker, K.D.,Showalter, R.E.,Moomaw, E.W.,Gastinel, L.N.,Habuka, N.,Chen, X.,Maldonado, F.,Barker, J.E.,Bacquet, R.,Villafranca, J.E.
Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex.
Nature, 378:641-644, 1995

PubMed Abstract: Calcineurin (CaN) is a calcium- and calmodulin-dependent protein serine/threonine phosphate which is critical for several important cellular processes, including T-cell activation. CaN is the target of the immunosuppressive drugs cyclosporin A and FK506, which inhibit CaN after forming complexes with cytoplasmic binding proteins (cyclophilin and FKBP12, respectively). We report here the crystal structures of full-length human CaN at 2.1 A resolution and of the complex of human CaN with FKBP12-FK506 at 3.5 A resolution. In the native CaN structure, an auto-inhibitory element binds at the Zn/Fe-containing active site. The metal-site geometry and active-site water structure suggest a catalytic mechanism involving nucleophilic attack on the substrate phosphate by a metal-activated water molecule. In the FKBP12-FK506-CaN complex, the auto-inhibitory element is displaced from the active site. The site of binding of FKBP12-FK506 appears to be shared by other non-competitive inhibitors of calcineurin, including a natural anchoring protein.

PubMed: 8524402
DOI: 10.1038/378641a0

Experimental method

X-RAY DIFFRACTION (2.1 Å)