First Crystal Structure of a Medicinally Relevant Gold Protein Complex: Unexpected Binding of [Au(PEt3)]+ to Histidine
Juan Zou Dr.
Department of Chemistry The University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JJ (UK) Fax: (+44) 131-650-6452
Search for more papers by this authorPaul Taylor Dr.
Institute of Cell and Molecular Biology Michael Swann Building The University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JR (UK) Fax: (+44) 131-650-7055
Search for more papers by this authorJacqueline Dornan
Institute of Cell and Molecular Biology Michael Swann Building The University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JR (UK) Fax: (+44) 131-650-7055
Search for more papers by this authorStephen P. Robinson
Institute of Cell and Molecular Biology Michael Swann Building The University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JR (UK) Fax: (+44) 131-650-7055
Search for more papers by this authorMalcolm D. Walkinshaw Prof. Dr.
Institute of Cell and Molecular Biology Michael Swann Building The University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JR (UK) Fax: (+44) 131-650-7055
Search for more papers by this authorPeter J. Sadler Prof. Dr.
Department of Chemistry The University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JJ (UK) Fax: (+44) 131-650-6452
Search for more papers by this authorJuan Zou Dr.
Department of Chemistry The University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JJ (UK) Fax: (+44) 131-650-6452
Search for more papers by this authorPaul Taylor Dr.
Institute of Cell and Molecular Biology Michael Swann Building The University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JR (UK) Fax: (+44) 131-650-7055
Search for more papers by this authorJacqueline Dornan
Institute of Cell and Molecular Biology Michael Swann Building The University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JR (UK) Fax: (+44) 131-650-7055
Search for more papers by this authorStephen P. Robinson
Institute of Cell and Molecular Biology Michael Swann Building The University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JR (UK) Fax: (+44) 131-650-7055
Search for more papers by this authorMalcolm D. Walkinshaw Prof. Dr.
Institute of Cell and Molecular Biology Michael Swann Building The University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JR (UK) Fax: (+44) 131-650-7055
Search for more papers by this authorPeter J. Sadler Prof. Dr.
Department of Chemistry The University of Edinburgh, King's Buildings West Mains Road, Edinburgh EH9 3JJ (UK) Fax: (+44) 131-650-6452
Search for more papers by this authorWe thank the Wellcome Trust (Fellowship for J.Z.), BBSRC, CLRC, and EPSRC for their support for this work, Dr. Adam Gouldsworthy and Mr. Mark Scott (Edinburgh Centre for Protein Technology) for their assistance with LC-ESI-MS, Drs. George Kontopidis, Su-ying Wu, and Hongzhe Sun for their valuable suggestions, discussion, and technical assistance.
Abstract
Unexpectedly, not interested in sulfur: the antiarthritic complex [Au(PEt3)Cl] (1) reacts with crystals of cyclophilin-3 (Cyp-3), a peptidyl prolyl isomerase enzyme linked to cellular stress responses, to form an Nε-bound [AuPEt3]+ adduct with the active site residue His 133, despite the presence of four Cys thiol groups in the protein. Complex 1 is a potent inhibitor of the enzyme (IC50=14 nM).
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