2025-11-29_00000227|ligand|9V6J

Structure-Guided Design of Picomolar-level Macrocyclic TRPC5 Channel Inhibitors with Antidepressant Activity; Electron microscopy 3.23Å
Protein #1 975 residues (71% resolved)

MAQLYYKKVNYSPYRDRIPLQIVRAETELSAEEKAFLSAVEKGDYATVKQALQEAEIYYNVNINCMDPLGRSALLIAIENENLEIMELLLNHSVYVGDALLYAIRKEVVGAVELLLSYRKPSGEKQVPTLMMDTQFSEFTPDITPIMLAAHTNNYEIIKLLVQKRVTIPRPHQIRCNCVECVSSSEVDSLRHSRSRLNIYKALASPSLIALSSEDPILTAFRLGWELKELSKVENEFKAEYEELSQQCKLFAKDLLDQARSSRELEIILNHRDDHSEELDPQKYHDLAKLKVAIKYHQKEFVAQPNCQQLLATLWYDGFPGWRRKHWVVKLLTCMTIGFLFPMLSIAYLISPRSNLGLFIKKPFIKFICHTASYLTFLFMLLLASQHIVRTDLHVQGPPPTVVEWMILPWVLGFIWGEIKEMWDGGFTEYIHDWWNLMDFAMNSLYLATISLKIVAYVKYNGSRPREEWEMWHPTLIAEALFAISNILSSLRLISLFTANSHLGPLQISLGRMLLDILKFLFIYCLVLLAFANGLNQLYFYYETRAIDEPNNCKGIRCEKQNNAFSTLFETLQSLFWSVFGLLNLYVTNVKARHEFTEFVGATMFGTYNVISLVVLLNMLIAMMNNSYQLIADHADIEWKFARTKLWMSYFDEGGTLPPPFNIIPSPKSFLYLGNWFNNTFCPKRDPDGRRRRHNLRSFTERHADSLIQNQHYQEVIRNLVKRYVAAMIRNSKTNEGLTEENFKELKQDISSFRYEVLDLLGNRKHPRRSLSTSSADFSQRDDTNDGSGGARAKSKSVSFNVGCKKKACHGAPLIRTVPRASGAQGKPKSESSSKRSFMGPSFKKLGLFFSKFNGQTSEPTSEPMYTISDGIAQQHCMWQDIRYSQMEKGKAEACSQSQMNLGEVELGEIRGAAARSSECPLACSSSLHCASGICSSNSKLLDSSEDVFETWGEACDLLMHKWGDGQEEQVTTRL

MAQLYYKKVNYSPYRDRIPLQIVRAETELSAEEKAFLSAVEKGDYATVKQALQEAEIYYNVNINCMDPLGRSALLIAIENENLEIMELLLNHSVYVGDALLYAIRKEVVGAVELLLSYRKPSGEKQVPTLMMDTQFSEFTPDITPIMLAAHTNNYEIIKLLVQKRVTIPRPHQIRCNCVECVSSSEVDSLRHSRSRLNIYKALASPSLIALSSEDPILTAFRLGWELKELSKVENEFKAEYEELSQQCKLFAKDLLDQARSSRELEIILNHRDDHSEELDPQKYHDLAKLKVAIKYHQKEFVAQPNCQQLLATLWYDGFPGWRRKHWVVKLLTCMTIGFLFPMLSIAYLISPRSNLGLFIKKPFIKFICHTASYLTFLFMLLLASQHIVRTDLHVQGPPPTVVEWMILPWVLGFIWGEIKEMWDGGFTEYIHDWWNLMDFAMNSLYLATISLKIVAYVKYNGSRPREEWEMWHPTLIAEALFAISNILSSLRLISLFTANSHLGPLQISLGRMLLDILKFLFIYCLVLLAFANGLNQLYFYYETRAIDEPNNCKGIRCEKQNNAFSTLFETLQSLFWSVFGLLNLYVTNVKARHEFTEFVGATMFGTYNVISLVVLLNMLIAMMNNSYQLIADHADIEWKFARTKLWMSYFDEGGTLPPPFNIIPSPKSFLYLGNWFNNTFCPKRDPDGRRRRHNLRSFTERHADSLIQNQHYQEVIRNLVKRYVAAMIRNSKTNEGLTEENFKELKQDISSFRYEVLDLLGNRKHPRRSLSTSSADFSQRDDTNDGSGGARAKSKSVSFNVGCKKKACHGAPLIRTVPRASGAQGKPKSESSSKRSFMGPSFKKLGLFFSKFNGQTSEPTSEPMYTISDGIAQQHCMWQDIRYSQMEKGKAEACSQSQMNLGEVELGEIRGAAARSSECPLACSSSLHCASGICSSNSKLLDSSEDVFETWGEACDLLMHKWGDGQEEQVTTRL
Non polymer #2 A1EH7

InChI=1S/C27H28ClFN4O5/c28-19-8-6-18(7-9-19)17-33-23-24-30-26(33)38-20-10-11-21(29)22(16-20)37-15-4-2-1-3-12-31(24)27(36)32(25(23)35)13-5-14-34/h6-11,16,34H,1-5,12-15,17H2

c1cc(ccc1Cn2c3c4nc2Oc5ccc(c(c5)OCCCCCCN4C(=O)N(C3=O)CCCO)F)Cl
Non polymer #3 CA

InChI=1S/Ca/q+2

[Ca+2]
Non polymer #4 ZN

InChI=1S/Zn/q+2

[Zn+2]
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Reference