Versatility of signal transduction encoded in dimeric adenylyl cyclases.
Out of six classes of adenylyl cyclases all class III enzymes convert ATP to cAMP in a catalytic centre moulded into an interface of bacterial homodimers and eukaryotic (pseudo)heterodimers. Formation of the catalytic centre, therefore, requires meticulous coordination of catalytic amino acids. Regulation of adenylyl cyclase activity via subtle or profound reorientation processes within the dimer interface is demonstrated on the basis of four class III adenylyl cyclase structures, a mammalian heterodimer, a mycobacterial holoenzyme that is pH regulated, another mycobacterial isoform that reorients upon substrate binding and a cyanobacterial cyclase activated by bicarbonate. Thus the interface of class III adenylyl cyclases is a like scaffold used in the regulation of activity by intrinsic and extrinsic signaling modules.
Linder
Jürgen U
JU
Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA. jul2015@med.cornell.edu
Schultz
Joachim E
JE
D000262:Adenylyl Cyclases / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001639:Bicarbonates / Q000378:metabolism; D055162:Biocatalysis; D006863:Hydrogen-Ion Concentration; D008322:Mammals / Q000378:metabolism; D008566:Membranes / Q000201:enzymology; D009161:Mycobacterium / Q000201:enzymology; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D053545:Spirulina / Q000201:enzymology*; D013379:Substrate Specificity
D001426:Bacterial Proteins; D001639:Bicarbonates; D000262:Adenylyl Cyclases