5x33
From Proteopedia
Leukotriene B4 receptor BLT1 in complex with BIIL260
Structural highlights
FunctionQ9WTK1_CAVPO A0A097J792_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[HAMAP-Rule:MF_04110] Publication Abstract from PubMedMost G-protein-coupled receptors (GPCRs) are stabilized in common in the inactive state by the formation of the sodium ion-centered water cluster with the conserved Asp(2.50) inside the seven-transmembrane domain. We determined the crystal structure of the leukotriene B4 (LTB4) receptor BLT1 bound with BIIL260, a chemical bearing a benzamidine moiety. Surprisingly, the amidine group occupies the sodium ion and water locations, interacts with D66(2.50), and mimics the entire sodium ion-centered water cluster. Thus, BLT1 is fixed in the inactive state, and the transmembrane helices cannot change their conformations to form the active state. Moreover, the benzamidine molecule alone serves as a negative allosteric modulator for BLT1. As the residues involved in the benzamidine binding are widely conserved among GPCRs, the unprecedented inverse-agonist mechanism by the benzamidine moiety could be adapted to other GPCRs. Consequently, the present structure will enable the rational development of inverse agonists specific for each GPCR. Na(+)-mimicking ligands stabilize the inactive state of leukotriene B4 receptor BLT1.,Hori T, Okuno T, Hirata K, Yamashita K, Kawano Y, Yamamoto M, Hato M, Nakamura M, Shimizu T, Yokomizo T, Miyano M, Yokoyama S Nat Chem Biol. 2018 Jan 8. pii: nchembio.2547. doi: 10.1038/nchembio.2547. PMID:29309055[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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