EzCatDB: M00102

DB codeM00102
RLCP classification1.15.39000.353
CATH domainDomain 12.70.150.10
Domain 21.20.1110.10
Domain 33.40.1110.10
Domain 43.40.50.1000Catalytic domain
E.C.3.6.3.8
CSA1eul

CATH domainRelated DB codes (homologues)
3.40.50.1000D00248

Enzyme Name
Swiss-protKEGG

P04191
Protein nameSarcoplasmic/endoplasmic reticulum calcium ATPase 1Ca2+-transporting ATPase
sarcoplasmic reticulum ATPase
sarco(endo)plasmic reticulum Ca2+-ATPase
calcium pump
Ca2+-pumping ATPase
plasma membrane Ca-ATPase
SynonymsSERCA1
EC 3.6.3.8
Calcium pump 1
Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform
SR Ca(2+)-ATPase 1
Endoplasmic reticulum class 1/2 Ca(2+) ATPase


Swiss-prot:Accession NumberP04191
Entry nameAT2A1_RABIT
ActivityATP + H(2)O + Ca(2+)(Cis) = ADP + phosphate + Ca(2+)(Trans).
SubunitAssociated with sarcolipin (SLN) (By similarity) and phospholamban (PLN).
Subcellular locationEndoplasmic reticulum membrane, Multi-pass membrane protein. Sarcoplasmic reticulum membrane, Multi-pass membrane protein.
Cofactor


CofactorsSubstratesProducts
KEGG-idC00305C00002C00001C00076C00008C00009C00076
CompoundmagnesiumATPH2OCa2+(cis)ADPOrthophosphateCa2+(trans)
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideH2Odivalent metal (Ca2+, Mg2+)amine group,nucleotidephosphate group/phosphate iondivalent metal (Ca2+, Mg2+)
1eulA01UnboundUnbound
UnboundUnboundUnboundUnbound
1iwoA01UnboundUnbound
UnboundUnboundUnboundUnbound
1iwoB01UnboundUnbound
UnboundUnboundUnboundUnbound
1kjuA01UnboundUnbound
UnboundUnboundUnboundUnbound
1eulA02UnboundUnbound
Bound:2x_CAUnboundUnboundBound:2x_CA
1iwoA02UnboundUnbound
UnboundUnboundUnboundUnbound
1iwoB02UnboundUnbound
UnboundUnboundUnboundUnbound
1kjuA02UnboundUnbound
UnboundUnboundUnboundUnbound
1eulA03UnboundUnbound
UnboundUnboundUnboundUnbound
1iwoA03UnboundUnbound
UnboundUnboundUnboundUnbound
1iwoB03UnboundUnbound
UnboundUnboundUnboundUnbound
1kjuA03UnboundUnbound
UnboundUnboundUnboundUnbound
1eulA04UnboundUnbound
UnboundUnboundUnboundUnbound
1iwoA04UnboundUnbound
UnboundUnboundUnboundUnbound
1iwoB04UnboundUnbound
UnboundUnboundUnboundUnbound
1kjuA04UnboundUnbound
UnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot, PDB
pdbCofactor-binding residuesModified residues
1eulA01

1iwoA01

1iwoB01

1kjuA01

1eulA02ASN 768;GLU 771;THR 799;ASP 800;GLU 908(Ca-1 binding);VAL 304;ALA 305;ILE 307;GLU 309;ASN 796;ASP 800(Ca-2 binding)

1iwoA02ASN 768;GLU 771;THR 799;ASP 800;GLU 908(Ca-1 binding);VAL 304;ALA 305;ILE 307;GLU 309;ASN 796;ASP 800(Ca-2 binding)

1iwoB02ASN 768;GLU 771;THR 799;ASP 800;GLU 908(Ca-1 binding);VAL 304;ALA 305;ILE 307;GLU 309;ASN 796;ASP 800(Ca-2 binding)

1kjuA02ASN 768;GLU 771;THR 799;ASP 800;GLU 908(Ca-1 binding);VAL 304;ALA 305;ILE 307;GLU 309;ASN 796;ASP 800(Ca-2 binding)

1eulA03

1iwoA03

1iwoB03

1kjuA03

1eulA04ASP 703;ASP 707(Mg binding)
ASP 351(phosphorylation)
1iwoA04ASP 703;ASP 707(Mg binding)
ASP 351(phosphorylation)
1iwoB04ASP 703;ASP 707(Mg binding)
ASP 351(phosphorylation)
1kjuA04ASP 703;ASP 707(Mg binding)
ASP 351(phosphorylation)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.651-652
[4]p.667-671, p.673-676
[8]Fig.32
[9]p.207, Fig.72
[11]Fig.5, p.426-4292
[15]p.452-453, p.459-462

references
[1]
CommentsX-ray crystallography (2.6 Angstroms)
Medline ID20320311
PubMed ID10864315
JournalNature
Year2000
Volume405
Pages647-655
AuthorsToyoshima C, Nakasako M, Nomura H, Ogawa H
TitleCrystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution.
[2]
PubMed ID10998362
JournalBiochem J
Year2000
Volume351
Pages195-205
AuthorsNegash S, Yao Q, Sun H, Li J, Bigelow DJ, Squier TC
TitlePhospholamban remains associated with the Ca2+- and Mg2+-dependent ATPase following phosphorylation by cAMP-dependent protein kinase.
[3]
PubMed ID11311132
JournalBiochem J
Year2001
Volume355
Pages699-706
AuthorsSharma P, Patchell VB, Gao Y, Evans JS, Levine BA
TitleCytoplasmic interactions between phospholamban residues 1-20 and the calcium-activated ATPase of the sarcoplasmic reticulum.
[4]
PubMed ID11389676
JournalBiochem J
Year2001
Volume356
Pages665-83
AuthorsLee AG, East JM
TitleWhat the structure of a calcium pump tells us about its mechanism.
[5]
Commentsmutation analysis
PubMed ID11438551
JournalJ Biol Chem
Year2001
Volume276
Pages35741-35750
AuthorsClausen JD, McIntosh DB, Woolley DG, Andersen JP
TitleImportance of Thr-353 of the conserved phosphorylation loop of the sarcoplasmic reticulum Ca2+-ATPase in MgATP binding and catalytic activity.
[6]
PubMed ID11526231
JournalProc Natl Acad Sci U S A
Year2001
Volume98
Pages10061-6
AuthorsAsahi M, Green NM, Kurzydlowski K, Tada M, MacLennan DH
TitlePhospholamban domain IB forms an interaction site with the loop between transmembrane helices M6 and M7 of sarco(endo)plasmic reticulum Ca2+ ATPases.
[7]
PubMed ID11544263
JournalJ Biol Chem
Year2001
Volume276
Pages42793-800
AuthorsReis M, Farage M, de Souza AC, de Meis L
TitleCorrelation between uncoupled ATP hydrolysis and heat production by the sarcoplasmic reticulum Ca2+-ATPase: coupling effect of fluoride.
[8]
PubMed ID11557055
JournalFEBS Lett
Year2001
Volume505
Pages129-35
AuthorsDanko S, Yamasaki K, Daiho T, Suzuki H, Toyoshima C
TitleOrganization of cytoplasmic domains of sarcoplasmic reticulum Ca(2+)-ATPase in E(1)P and E(1)ATP states: a limited proteolysis study.
[9]
Commentsstructural model, catalysis
PubMed ID11829513
JournalJ Mol Biol
Year2002
Volume316
Pages201-211
AuthorsXu C, Rice WJ, He W, Stokes DL
TitleA structural model for the catalytic cycle of Ca(2+)-ATPase.
[10]
PubMed ID11841218
JournalBiochemistry
Year2002
Volume41
Pages2264-72
AuthorsHua S, Ma H, Lewis D, Inesi G, Toyoshima C
TitleFunctional role of "N" (nucleotide) and "P" (phosphorylation) domain interactions in the sarcoplasmic reticulum (SERCA) ATPase.
[11]
PubMed ID12051918
JournalJ Mol Biol
Year2002
Volume319
Pages421-31
AuthorsWang W, Cho HS, Kim R, Jancarik J, Yokota H, Nguyen HH, Grigoriev IV, Wemmer DE, Kim SH
TitleStructural characterization of the reaction pathway in phosphoserine phosphatase: crystallographic "snapshots" of intermediate states.
[12]
PubMed ID12163080
JournalCurr Opin Struct Biol
Year2002
Volume12
Pages547-54
AuthorsLee AG
TitleA calcium pump made visible.
[13]
PubMed ID12167852
JournalNature
Year2002
Volume418
Pages605-11
AuthorsToyoshima C, Nomura H
TitleStructural changes in the calcium pump accompanying the dissociation of calcium.
[14]
PubMed ID12172642
JournalJ Membr Biol
Year2002
Volume188
Pages1-9
Authorsde Meis L
TitleCa2+-ATPases (SERCA): energy transduction and heat production in transport ATPases.
[15]
PubMed ID12598367
JournalAnnu Rev Biophys Biomol Struct
Year2003
Volume32
Pages445-68
AuthorsStokes DL, Green NM
TitleStructure and function of the calcium pump.
[16]
PubMed ID12829699
JournalJ Biol Chem
Year2003
Volume278
Pages35798-804
AuthorsPadanyi R, Paszty K, Penheiter AR, Filoteo AG, Penniston JT, Enyedi A
TitleIntramolecular interactions of the regulatory region with the catalytic core in the plasma membrane calcium pump.
[17]
PubMed ID14630328
JournalFEBS Lett
Year2003
Volume555
Pages106-10
AuthorsToyoshima C, Nomura H, Sugita Y
TitleStructural basis of ion pumping by Ca(2+)-ATPase of sarcoplasmic reticulum.

comments
This belongs to the cation transport ATPases family (E1-E2 ATPases).
Although the catalytic mechanism of the homologous enzyme of this ATPase, phosphoserine phosphatase, have been elucidated and considered to be similar to its own mechanism, the corresponding residues to general acid/base are not found [11].
However, Asp351 acts as a nucleophile to form phosho-aspartyl enzyme intermediate through associative mechanism (SN2-like reaction) ([15] & [22]). During this reaction, magnesium ion, which might be ligated to Asp351 and transferred phosphate group, may assist the nucleophilic attack, according to the literature for the homologous enzyme, phosphoserine phosphatase [22].
At the next stage, a water molecule will attack the acyl-phosphate. However, the general base, which will activate the hydrolytic water, has not been reported.

createdupdated
2002-07-092009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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