4J2T

Inhibitor-bound Ca2+ ATPase

Summary for 4J2T

• Entry DOI: 10.2210/pdb4j2t/pdb
• Related: 2C8K 3N5K 3NAL 3NAM 3NAN
• Descriptor: SERCA1a, (3S,3aR,4S,6S,6aR,7S,8S,9bS)-6-(acetyloxy)-3a,4-bis(butanoyloxy)-3-hydroxy-3,6,9-trimethyl-8-{[(2E)-2-methylbut-2-enoyl]oxy}-2-oxo-2,3,3a,4,5,6,6a,7,8,9b-decahydroazuleno[4,5-b]furan-7-yl octanoate, PHOSPHATIDYLETHANOLAMINE, ... (5 entities in total)
• Functional Keywords: p-type atpase, calcium transport, thapsigargin analog, sarco(endo)plasmic reticulum, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Oryctolagus cuniculus (rabbit)
• Cellular location: Membrane ; Multi-pass membrane protein : B6CAM1
• Total number of polymer chains: 1
• Total formula weight: 111096.56

Authors

Paulsen, E.S.,Villadsen, J.,Tenori, E.,Liu, H.,Lie, M.A.,Bonde, D.F.,Bublitz, M.,Olesen, C.,Autzen, H.E.,Dach, I.,Sehgal, P.,Moller, J.V.,Schiott, B.,Nissen, P.,Christensen, S.B. (deposition date: 2013-02-05, release date: 2013-06-19, Last modification date: 2024-10-16)

Primary citation

Paulsen, E.S.,Villadsen, J.,Tenori, E.,Liu, H.,Bonde, D.F.,Lie, M.A.,Bublitz, M.,Olesen, C.,Autzen, H.E.,Dach, I.,Sehgal, P.,Nissen, P.,Moller, J.V.,Schiott, B.,Christensen, S.B.
Water-mediated interactions influence the binding of thapsigargin to sarco/endoplasmic reticulum calcium adenosinetriphosphatase.
J.Med.Chem., 56:3609-3619, 2013

PubMed Abstract: A crystal structure suggests four water molecules are present in the binding cavity of thapsigargin in sarco/endoplasmic reticulum calcium ATPase (SERCA). Computational chemistry indicates that three of these water molecules mediate an extensive hydrogen-bonding network between thapsigargin and the backbone of SERCA. The orientation of the thapsigargin molecule in SERCA is crucially dependent on these interactions. The hypothesis has been verified by measuring the affinity of newly synthesized model compounds, which are prevented from participating in such water-mediated interactions as hydrogen-bond donors.

PubMed: 23574308
DOI: 10.1021/jm4001083

Experimental method

X-RAY DIFFRACTION (3.2 Å)