Palmer Taylor Sandra & Monroe Trout Professor of Pharmacology Dean, Skaggs School of Pharmacy & Pharmaceutical Sciences Associate Vice Chancellor for Health Sciences - SPPS Phone: 858-534-1366 Fax: 858-534-8248 E-mail: pwtaylor@ucsd.edu

Key Words: Neuropharmacology; Gene Expression; Cholinergic Receptors; Acetylcholinesterase

Dr. Palmer Taylor's research has been directed to the structures, recognition capacities and regulation of expression of proteins governing neurotransmission in cholinergic synapses. His group cloned the first acetylcholinesterase (AChE) gene over 20 years ago, and this was followed by analysis of its genomic DNA to delineate regulatory regions, the multiple splicing options and gene expression profiles in nerve and muscle. His studies of AChE structure and its complexes by crystallographic and fluorescence methods, characterizing a peripheral site on AChE and the demonstrating flexibility of the active center gorge, provided the basis for collaborative studies with Barry Sharpless' group employing freeze-frame, click chemistry. The very biological target itself (AChE) is used as the template in the synthesis of high affinity, selective inhibitors. Taylor's long standing work with nicotinic acetylcholine receptors (nAChR) defined ligand specificity in relation to state functions for receptor activation and desensitization and identified the structural determinants on nAChR governing ligand and peptide toxin specificity. More recently, his studies have been directed to the acetylcholine binding protein, a soluble surrogate of the receptor, whereby his group in collaboration with others, employed physical methods of fluorescence anisotropy decay, NMR, x-ray crystallography and denterium hydrogen exchange to examine structure and selectivity of the ligand binding sites. Finally, through collaborative endeavors, Taylor's group have uncovered much of what is known about the structure of neuroligin, a synaptic adhesion molecule homologous to AChE. Their structural studies on neuroligin have uncovered alterations in processing and folding associated with mutations found in the autistic spectral disorders.

Recent Publications

Schumacher, M., Camp, S., Maulet, Y., Newton, M., MacPhee-Quigley, K., Taylor, S.S., Friedmann, T. and Taylor, P. Primary Structure of Torpedo californica Acetylcholinesterase Deduced from its cDNA Sequence. Nature 319:407-409 (1986).

Kreienkamp. H.-J., Maeda, R.K., Sine, S.M. and Taylor, P. Intersubunit Contacts Governing Assembly of the Mammalian Nicotinic Acetylcholine Receptor. Neuron 14:635-644 (1995).

Bourne, Y., Kolb, H.C., Radic Z., Sharpless, K.B., Taylor, P. and Marchot, P. Freeze-frame Inhibitor Captures Acetylcholinesterase in a Unique Conformation. Proc. Natl. Acad. Sci., 101:1449-1454 (2004).

Hansen, S.B., Talley, T.T., Radic, Z. and Taylor, P. Structural and Ligand Recognition Characteristics of an Acetylcholine-binding Protein from Aplysia californica. J. Biol. Chem., 279:24197-24202 (2004).

Hansen, S.B., Sulzenbacher, G., Huxford, T., Marchot, P., Taylor, P. and Bourne, Y. Structures of Aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations. The EMBO J., 24:3635-3646 (2005).

De Jaco, A., Comoletti, D., Kovarik, Z., Gaietta, G., Radic, Z., Lockridge, O., Ellisman, M.H. and Taylor, P. A Mutation Linked with Autism Reveals a Common Mechanism of Endoplasmic Reticulum Retention for the a,ß-Hydrolase Fold Protein Family. J. Biol. Chem., 281:9667-9676 (2006).

Talley, T.T., Yalda, S., Ho, K-Y, Tor, Y., Soti, F.S., Kem, W.R. and Taylor, P. Spectroscopic Analysis of Benzylidene Anabaseine Complexes with Acetylcholine Binding Proteins as Models for Ligand-Nicotinic Receptor Interactions. Biochemistry, 45:8894-8902 (2006).