5iv4 | pdb_00005iv4

Crystal structure of the human soluble cyclase in complex with the allosteric inhibitor LRE1

spinqualitylabelsall models 5iv4, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5iv4 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CL, DMS, EDO, GOL, LRI, PEG NonStd Res: CME Activity: Adenylate cyclase, with EC number 4.6.1.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [ADCYA_HUMAN] Idiopathic hypercalciuria. Disease susceptibility is associated with variations affecting the gene represented in this entry. Function [ADCYA_HUMAN] Soluble adenylyl cyclase that has a critical role in mammalian spermatogenesis. Produces the cAMP which mediates in part the cAMP-responsive nuclear factors indispensable for maturation of sperm in the epididymis. Induces capacitation, the maturational process that sperm undergo prior to fertilization. May be the bicarbonate sensor. Involved in ciliary beat regulation. Publication Abstract from PubMed The prototypical second messenger cAMP regulates a wide variety of physiological processes. It can simultaneously mediate diverse functions by acting locally in independently regulated microdomains. In mammalian cells, two types of adenylyl cyclase generate cAMP: G-protein-regulated transmembrane adenylyl cyclases and bicarbonate-, calcium- and ATP-regulated soluble adenylyl cyclase (sAC). Because each type of cyclase regulates distinct microdomains, methods to distinguish between them are needed to understand cAMP signaling. We developed a mass-spectrometry-based adenylyl cyclase assay, which we used to identify a new sAC-specific inhibitor, LRE1. LRE1 bound to the bicarbonate activator binding site and inhibited sAC via a unique allosteric mechanism. LRE1 prevented sAC-dependent processes in cellular and physiological systems, and it will facilitate exploration of the therapeutic potential of sAC inhibition. Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase.,Ramos-Espiritu L, Kleinboelting S, Navarrete FA, Alvau A, Visconti PE, Valsecchi F, Starkov A, Manfredi G, Buck H, Adura C, Zippin JH, van den Heuvel J, Glickman JF, Steegborn C, Levin LR, Buck J Nat Chem Biol. 2016 Aug 22. doi: 10.1038/nchembio.2151. PMID:27547922 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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