6f3w

Backbone structure of free bradykinin (BK) in DDM/CHS detergent micelle determined by MAS SSNMR

spinqualitylabelsall models 6f3w, 10 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6f3w is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 6f3v, 6f27 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [KNG1_HUMAN] Congenital high-molecular-weight kininogen deficiency. The disease is caused by mutations affecting the gene represented in this entry. Function [KNG1_HUMAN] (1) Kininogens are inhibitors of thiol proteases; (2) HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin-induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from HMW-kininogen shows a variety of physiological effects: (4A) influence in smooth muscle contraction, (4B) induction of hypotension, (4C) natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it is a mediator of inflammation and causes (4E1) increase in vascular permeability, (4E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (4F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW-kininogen is in contrast to HMW-kininogen not involved in blood clotting. Publication Abstract from PubMed G-protein-coupled receptors (GPCRs) are the most important signal transducers in higher eukaryotes. Despite considerable progress, the molecular basis of subtype-specific ligand selectivity, especially for peptide receptors, remains unknown. Here, by integrating DNP-enhanced solid-state NMR spectroscopy with advanced molecular modeling and docking, the mechanism of the subtype selectivity of human bradykinin receptors for their peptide agonists has been resolved. The conserved middle segments of the bound peptides show distinct conformations that result in different presentations of their N and C termini toward their receptors. Analysis of the peptide-receptor interfaces reveals that the charged N-terminal residues of the peptides are mainly selected through electrostatic interactions, whereas the C-terminal segments are recognized via both conformations and interactions. The detailed molecular picture obtained by this approach opens a new gateway for exploring the complex conformational and chemical space of peptides and peptide analogs for designing GPCR subtype-selective biochemical tools and drugs. The molecular basis of subtype selectivity of human kinin G-protein-coupled receptors.,Joedicke L, Mao J, Kuenze G, Reinhart C, Kalavacherla T, Jonker HRA, Richter C, Schwalbe H, Meiler J, Preu J, Michel H, Glaubitz C Nat Chem Biol. 2018 Jan 15. pii: nchembio.2551. doi: 10.1038/nchembio.2551. PMID:29334381 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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