11CK
Structure of human TRPV1 in complex with 6-Iodo-CAP (CAY10448)
This is a non-PDB format compatible entry.
Summary for 11CK
| Entry DOI | 10.2210/pdb11ck/pdb |
| EMDB information | 75617 |
| Descriptor | Transient receptor potential cation channel subfamily V member 1, N-[(4-hydroxy-2-iodo-5-methoxyphenyl)methyl]-8-methylnonanamide (2 entities in total) |
| Functional Keywords | membrane protein, ion channel, trpv1, mavatrep, asivatrep, jnj-17203212, cay10448, small molecule, pain, thermosensing, gdn, antagonist |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 498859.17 |
| Authors | |
| Primary citation | Lopez, K.E.,Paduda, A.S.,Derrick, M.J.,Van Horn, W.D. TRPV1 antagonism occurs through diverse structural mechanisms. Biorxiv, 2026 Cited by PubMed Abstract: Transient receptor potential vanilloid 1 (TRPV1) ion channel mediates thermosensation and pain and is a target for non-addictive analgesics; however, clinical candidates have failed due to thermoregulatory side effects. Limited structural data for human TRPV1 (hTRPV1) bound to clinically relevant antagonists has constrained mechanistic insight. Using chemoinformatics-informed cryo-EM and BRET assays, we define the structural basis of antagonism across diverse chemotypes, including failed clinical compounds. A structure of hTRPV1 bound to 6-iodo-dihydrocapsaicin shows how a single substitution converts an agonist into an antagonist. Additional structures with Asivatrep, Mavatrep, and JNJ-17203212 reveal vanilloid pocket plasticity and divergent interaction networks, including lipid co-binding. Despite this diversity, antagonists converge on a conserved inhibited state, showing high potency is maintained across flexible binding modes. These findings redefine our understanding of hTRPV1 antagonism and illustrate how chemically diverse ligands stabilize an inhibited state in polymodal ion channels, laying groundwork for next-generation analgesics with improved safety. PubMed: 42094379DOI: 10.64898/2026.04.27.721197 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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