2zmh | pdb_00002zmh

Crystal Structure of Rat Vitamin D Receptor Bound to Adamantyl Vitamin D Analogs: Structural Basis for Vitamin D Receptor Antagonism and/or Partial Agonism

spinqualitylabelsall models 2zmh, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2zmh is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NYA Related: 2zmi, 2zmj Gene: Vdr, Nr1i1 (Rattus norvegicus) Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The X-ray crystal structures of the rat VDR ligand-binding domain complexed with 19-norvitamin D compounds that contain an adamantyl substituent at the side-chain terminus, 2a (ADTT), 2b (ADNY), and 2c (ADMI4) and a coactivator peptide derived from DRIP205 are reported. These compounds show a series of partial agonistic (10-75% efficacy)/antagonistic activities. All of these complexed receptors are crystallized in the canonical active conformation, regardless of their activity profiles. The bulky adamantyl side chain does not crowd helix 12 but protrudes into the gap formed by helix 11, loop 11-12, helix 3, and loop 6-7, thereby widening the ligand binding pocket. We suggest that these structural changes destabilize the active protein conformation and reduce its contribution to equilibrium among the active and inactive conformations. The coactivator peptide traps the minor active conformation, and the equilibrium shifts to the active conformation. As a result, these ligands show partial agonistic activities. Crystal Structures of Rat Vitamin D Receptor Bound to Adamantyl Vitamin D Analogs: Structural Basis for Vitamin D Receptor Antagonism and Partial Agonism.,Nakabayashi M, Yamada S, Yoshimoto N, Tanaka T, Igarashi M, Ikura T, Ito N, Makishima M, Tokiwa H, Deluca HF, Shimizu M J Med Chem. 2008 Aug 19. PMID:18710208 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Sandbox vdr Vitamin D receptor

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