4OYB
Crystal Structure Analysis of the solAC
Summary for 4OYB
| Entry DOI | 10.2210/pdb4oyb/pdb |
| Related | 4OYA 4OYI 4OYM 4OYO 4OYP 4OYW 4OYX 4OYZ 4OZ2 4OZ3 |
| Descriptor | Adenylate cyclase type 10, GLYCEROL, ethyl 2-[3-[(4-azanyl-1,2,5-oxadiazol-3-yl)carbonyl]phenoxy]ethanoate, ... (4 entities in total) |
| Functional Keywords | lyase |
| Biological source | Homo sapiens (Human) |
| Cellular location | Cell membrane; Peripheral membrane protein; Cytoplasmic side: Q96PN6 |
| Total number of polymer chains | 1 |
| Total formula weight | 53850.18 |
| Authors | Vinkovic, M. (deposition date: 2014-02-11, release date: 2014-04-02, Last modification date: 2024-11-20) |
| Primary citation | Saalau-Bethell, S.M.,Berdini, V.,Cleasby, A.,Congreve, M.,Coyle, J.E.,Lock, V.,Murray, C.W.,O'Brien, M.A.,Rich, S.J.,Sambrook, T.,Vinkovic, M.,Yon, J.R.,Jhoti, H. Crystal structure of human soluble adenylate cyclase reveals a distinct, highly flexible allosteric bicarbonate binding pocket. Chemmedchem, 9:823-832, 2014 Cited by PubMed Abstract: Soluble adenylate cyclases catalyse the synthesis of the second messenger cAMP through the cyclisation of ATP and are the only known enzymes to be directly activated by bicarbonate. Here, we report the first crystal structure of the human enzyme that reveals a pseudosymmetrical arrangement of two catalytic domains to produce a single competent active site and a novel discrete bicarbonate binding pocket. Crystal structures of the apo protein, the protein in complex with α,β-methylene adenosine 5'-triphosphate (AMPCPP) and calcium, with the allosteric activator bicarbonate, and also with a number of inhibitors identified using fragment screening, all show a flexible active site that undergoes significant conformational changes on binding of ligands. The resulting nanomolar-potent inhibitors that were developed bind at both the substrate binding pocket and the allosteric site, and can be used as chemical probes to further elucidate the function of this protein. PubMed: 24616449DOI: 10.1002/cmdc.201300480 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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