Structural and functional characterization of an anesthetic binding site in the second cysteine-rich domain of protein kinase Cδ*.

ABSTRACT: Elucidating the principles governing anesthetic-protein interactions requires structural determinations at high resolutions not yet achieved with ion channels. Protein kinase C (PKC) activity is modulated by general anesthetics. We solved the structure of the phorbol-binding domain (C1B) of PKCδ complexed with an ether (methoxymethylcycloprane) and with an alcohol (cyclopropylmethanol) at 1.36-Å resolution. The cyclopropane rings of both agents displace a single water molecule in a surface pocket adjacent to the phorbol-binding site, making van der Waals contacts with the backbone and/or side chains of residues Asn-237 to Ser-240. Surprisingly, two water molecules anchored in a hydrogen-bonded chain between Thr-242 and Lys-260 impart elasticity to one side of the binding pocket. The cyclop

SUBMITTER: Shanmugasundararaj S 

PROVIDER: S-EPMC3514512 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature