4z9g

Crystal structure of human corticotropin-releasing factor receptor 1 (CRF1R) in complex with the antagonist CP-376395 in a hexagonal setting with translational non-crystallographic symmetry

spinqualitylabelsall models 4z9g, resolution 3.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4z9g is a 3 chain structure with sequence from Enterobacteria phage RB51 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.183Å Ligands: 1Q5, OLA, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CRFR1_HUMAN Receptor for corticotropin releasing factor (CRH). Shows high-affinity CRF binding. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. C3V2B5_BPR51 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 PubMed The structural analysis of class B G protein-coupled receptors (GPCR), cell surface proteins responding to peptide hormones, has until recently been restricted to the extracellular domain (ECD). Corticotropin-releasing factor receptor type 1 (CRF1R) is a class B receptor mediating stress response and also considered a drug target for depression and anxiety. Here we report the crystal structure of the transmembrane domain of human CRF1R in complex with the small-molecule antagonist CP-376395 in a hexagonal setting with translational non-crystallographic symmetry. Molecular dynamics and metadynamics simulations on this novel structure and the existing TMD structure for CRF1R provides insight as to how the small molecule ligand gains access to the induced-fit allosteric binding site with implications for the observed selectivity against CRF2R. Furthermore, molecular dynamics simulations performed using a full-length receptor model point to key interactions between the ECD and extracellular loop 3 of the TMD providing insight into the full inactive state of multidomain class B GPCRs. Decoding Corticotropin-Releasing Factor Receptor Type 1 Crystal Structures.,Dore AS, Bortolato A, Hollenstein K, Cheng RKY, Read RJ, Marshall FH Curr Mol Pharmacol. 2017;10(4):334-344. doi: 10.2174/1874467210666170110114727. PMID:28183242 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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