4OYI: Human Solac Complexed With (4-amino-furazan-3-yl)-phenyl-methanone

Citation:
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 alpha,beta-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.
PDB ID: 4OYIDownload
MMDB ID: 118887
PDB Deposition Date: 2014/2/12
Updated in MMDB: 2014/04
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
Similar Structures:
Biological Unit for 4OYI: monomeric; determined by author
Molecular Components in 4OYI
Label Count Molecule
Protein (1 molecule)
1
Adenylate Cyclase Type 10(Gene symbol: ADCY10)
Molecule annotation
Chemicals (3 molecules)
1
1
2
2
* Click molecule labels to explore molecular sequence information.

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