5xgl | pdb_00005xgl

Co-crystal structure of Ac-AChBPP in complex with alpha-conotoxin LvIA

spinqualitylabelsall models 5xgl, resolution 3.44Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5xgl is a 10 chain structure with sequence from Aplysia californica and Conus lividus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.439Å Ligands: NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8WSF8_APLCA Publication Abstract from PubMed The alpha3* nAChRs, which are considered to be promising drug targets for problems such as pain, addiction, cardiovascular function, cognitive disorders etc., are found throughout the central and peripheral nervous system. The alpha-conotoxin (alpha-CTx) LvIA has been identified as the most selective inhibitor of alpha3beta2 nAChRs known to date, and it can distinguish the alpha3beta2 nAChR subtype from the alpha6/alpha3beta2beta3 and alpha3beta4 nAChR subtypes. However, the mechanism of its selectivity towards alpha3beta2, alpha6/alpha3beta2beta3, and alpha3beta4 nAChRs remains elusive. Here we report the co-crystal structure of LvIA in complex with Aplysia californica acetylcholine binding protein (Ac-AChBP) at a resolution of 3.4 A. Based on the structure of this complex, together with homology modeling based on other nAChR subtypes and binding affinity assays, we conclude that Asp-11 of LvIA plays an important role in the selectivity of LvIA towards alpha3beta2 and alpha3/alpha6beta2beta3 nAChRs by making a salt bridge with Lys-155 of the rat alpha3 subunit. Asn-9 lies within a hydrophobic pocket that is formed by Met-36, Thr-59, and Phe-119 of the rat beta2 subunit in the alpha3beta2 nAChR model, revealing the reason for its more potent selectivity towards the alpha3beta2 nAChR subtype. These results provide molecular insights that can be used to design ligands that selectively target alpha3beta2 nAChRs, with significant implications for the design of new therapeutic alpha-CTxs. The crystal structure of Ac-AChBP in complex with alpha-conotoxin LvIA reveals the mechanism of its selectivity towards different nAChR subtypes.,Xu M, Zhu X, Yu J, Yu J, Luo S, Wang X Protein Cell. 2017 Sep;8(9):675-685. doi: 10.1007/s13238-017-0426-2. Epub 2017, Jun 5. PMID:28585176 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholine binding protein 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA