2BY4

SR Ca(2+)-ATPase in the HnE2 state complexed with the thapsigargin derivative Boc-12ADT.

Summary for 2BY4

• Entry DOI: 10.2210/pdb2by4/pdb
• Related: 1FQU 1IWO 1KJU 1SU4 1T5S 1T5T 1VFP 1WPE 1WPG 1XP5 2AGV 2C88 2C8K 2C8L 2C9M
• Descriptor: SARCOPLASMIC/ENDOPLASMIC RETICULUM CALCIUM ATPASE 1, (3S,3AR,4S,6S,6AR,7S,8S,9BS)-6-(ACETYLOXY)-3,3A-DIHYDROXY-3,6,9-TRIMETHYL-8-{[(2Z)-2-METHYLBUT-2-ENOYL]OXY}-7-(OCTANOYLOXY)-2-OXO-2,3,3A,4,5,6,6A,7,8,9B-DECAHYDROAZULENO[4,5-B]FURAN-4-YL 12-[(TERT-BUTOXYCARBONYL)AMINO]DODECANOATE, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: serca, p-type atpase, ca2+-atpase, thapsigargin, prostate cancer, atp-binding, calcium, calcium transport, endoplasmic reticulum, hydrolase, ion transport, magnesium, metal-binding, multigene family, nucleotide-binding, phosphorylation, sarcoplasmic reticulum, transmembrane, transport
• Biological source: ORYCTOLAGUS CUNICULUS (RABBIT)
• Cellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein: P04191
• Total number of polymer chains: 1
• Total formula weight: 111057.48

Authors

Jensen, A.L.,Moller, J.V.,Soehoel, H.,Denmeade, S.R.,Isaacs, J.T.,Olsen, C.E.,Christensen, S.B.,Nissen, P. (deposition date: 2005-07-28, release date: 2006-04-07, Last modification date: 2024-11-06)

Primary citation

Soehoel, H.,Jensen, A.L.,Moller, J.V.,Nissen, P.,Denmeade, S.R.,Isaacs, J.T.,Olsen, C.E.,Christensen, S.B.
Natural Products as Starting Materials for Development of Second-Generation Serca Inhibitors Targeted Towards Prostate Cancer Cells
Bioorg.Med.Chem., 14:2810-, 2006

PubMed Abstract: An analysis of the binding of the 8-O-N-tert-butoxycarbonyl-12-aminododecanoyl derivative of 8-O-debutanoylthapsigargin to the target molecule, the SERCA pump, has revealed the importance of the length and flexibility of the side chain attached to O-8. Based on the analysis a series of analogues to the 2-unsubstituted analogue trilobolide has been constructed and shown to be equipotent with thapsigargin as SERCA inhibitors. Only the 12-Boc-aminododecaonoyl derivative, however, was found to be apoptotic.

PubMed: 16412648
DOI: 10.1016/J.BMC.2005.12.001

Experimental method

X-RAY DIFFRACTION (3.3 Å)