Mecanismo Atpasa De Calcio

The molecular path for Ca across the pump protein has been mapped and is shown in the cartoon of Figure 4: the first Ca would enter the binding cavity through gating residue Glu 309,positioning D800 to induce the rotation of M6 and, possibly, the straightening of the M5 helix. This would rearrange coordinating oxygens of site II to form a higher affinity site. At this point, the sidechain of E309 would cap site II Ca, mechanically transmitting the binding signal to the phosphorylation site _50 A° away. The straightening of the M5 helix would loosen up the compactconfiguration of the three cytoplasmic domains, which prevents the delivery of the ATP bound to the N domain to the catalytic D in the P domain. The binding of Ca also increases the tilting of the Ndomain, separating the P and A domains, permitting the delivery of ATP to the D315 phosphorylation site. The binding of ATP crosslinks the P and N domains, bending the former to make contact withthe A domain. The strain rotates the A domain, pulling up and bending the M1 helix, that closes the cytoplasmic E309 gate occluding the two bound Ca. The transfer of the phosphate of bound ATP tothe catalytic aspartate then dissociates bound ADP, opening the N-P domain interface. The rotation of the A domain rearranges helices M1-M6, opening the luminal gate for the release of theoccluded Ca. H+ and water molecules stabilize a second rotation of the A domain electrostatically locks it to the P domain, closing again the luminal gate. The A domain contains the highlyconserved TGES sequence: the rotation of the A domain retracts the side chain of E183 from the phosphorylation site, inducing a conformational
change in the TGES loop that permits the entrance of awater molecule in the phosphorylation site to hydrolyze the aspartylphosphate. The release of the phosphate (and of Mg) then relaxes the P domain completing the closing of the luminal gate.