GPCR Structure: Muscarinic M2 receptor
Another GPCR structure this week in Nature, this time, human muscarinic M2 receptor, complexed with an antagonist - 3-quinuclidinyl-benzilate - a controlled military incapacitation agent (CHEMBL12980); a link to the paper is here. A key difference to previously known structures is the large channel-like binding site. Coordinates are here PDBe:3uon
10 20 30 40 50 3uon ( 20 ) tfevvfivlvagslSlvTiigNilVmvSIkvnrhLqtvnnyflfSLAcAD aaaaaaaaaaaaaaaaaaaaaaaaaaaa 333 aaaaaaaaaaaaa 60 70 80 90 100 3uon ( 70 ) liiGvfSMnlytlytvigyWplgpvvÇdlWlalDYvVSNAsVmNLliiSf aaaaa aaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaa 110 120 130 140 150 3uon ( 120 ) dryfcvtkpltypvkrttkmAgmmiaaAwvlSfilwapaIlfwqfivgvr aaaaaaa 333 aaaaaaaaaaaaaaaaaaaaaaaaaaaaaa 160 170 180 190 200 3uon ( 170 ) tVedgeÇyIqffsnaavtfgtAiaaFylpviiMtvlywhisrasksri p 3333 aaaaaaaaaaa aaaaaaaaaaaaaaaaaa 210 220 230 240 250 3uon ( 378 ) ppsrekkvtrtilaIllaFiitWapYNvmVlintfçapçipntvwtiGyw aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaa 260 270 3uon ( 428 ) lCYinstiNpacYalcnatFkktfkhllm aaaa aaaaaaaaa aaaaaaaaaa
A K. Haga A A.C. Kruse A H. Asada A T. Yurugi-Kobayashi A M. Shiroishi A C. Zhang A W.I. Weis A T. Okada A B.K. Kobilka A T. Haga A T. Kobayashi %T Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist %J Nature
%V 482
%P 547-551 %O http://dx.doi.org/10.1038/nature10753 %D 2012
I only found the GPCR Network website today (doh!), there is a great tracking chart of ongoing structural programmes - so bring on the S1P and kappa opioid structures! (The picture above summarises their target selection)