PDBsum entry 3ba6

Hydrolase

PDB id: 3ba6

Contents

Protein chain

994 a.a. *

Ligands

AN2

Metals

_CA ×3

__K

Waters ×9

* Residue conservation analysis

PDB id:

3ba6

Name:

Hydrolase

Title:

Structure of the ca2e1p phosphoenzyme intermediate of the serca ca2+- atpase

Structure:

Sarcoplasmic/endoplasmic reticulum calcium atpase 1. Chain: a. Synonym: calcium pump 1, serca1, sr ca2+, -atpase 1, calcium- transporting atpase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform, endoplasmic reticulum class 1/2 ca2+, atpase. Ec: 3.6.3.8

Source:

Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986. Tissue: fast twitch skeletal muscle

Resolution:

2.80Å R-factor: 0.210 R-free: 0.288

Authors:

M.Picard,A.M.L.Winther,C.Olesen,C.Gyrup,J.P.Morth,C.Oxvig,J.V.Moller, P.Nissen

Key ref:

C.Olesen et al. (2007). The structural basis of calcium transport by the calcium pump. Nature, 450, 1036-1042. PubMed id: 18075584 DOI: 10.1038/nature06418

Date:

07-Nov-07 Release date: 18-Dec-07

Protein chain

P04191  (AT2A1_RABIT) -  Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 from Oryctolagus cuniculus

Seq: 1001 a.a.

Struc: 994 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.7.2.2.10 - P-type Ca(2+) transporter.
• Reaction: Ca²⁺(in) + ATP + H2O = Ca²⁺(out) + ADP + phosphate + H⁺

Ca(2+)(in) + ATP + H2O = Ca(2+)(out) (Bound ligand (Het Group name = AN2) matches with 92.86% similarity) + ADP + phosphate + H(+)

• Cofactor: Mg(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/nature06418

Nature 450:1036-1042 (2007)

PubMed id: 18075584

The structural basis of calcium transport by the calcium pump.

C.Olesen, M.Picard, A.M.Winther, C.Gyrup, J.P.Morth, C.Oxvig, J.V.Møller, P.Nissen.

ABSTRACT

The sarcoplasmic reticulum Ca2+-ATPase, a P-type ATPase, has a critical role in muscle function and metabolism. Here we present functional studies and three new crystal structures of the rabbit skeletal muscle Ca2+-ATPase, representing the phosphoenzyme intermediates associated with Ca2+ binding, Ca2+ translocation and dephosphorylation, that are based on complexes with a functional ATP analogue, beryllium fluoride and aluminium fluoride, respectively. The structures complete the cycle of nucleotide binding and cation transport of Ca2+-ATPase. Phosphorylation of the enzyme triggers the onset of a conformational change that leads to the opening of a luminal exit pathway defined by the transmembrane segments M1 through M6, which represent the canonical membrane domain of P-type pumps. Ca2+ release is promoted by translocation of the M4 helix, exposing Glu 309, Glu 771 and Asn 796 to the lumen. The mechanism explains how P-type ATPases are able to form the steep electrochemical gradients required for key functions in eukaryotic cells.

Selected figure(s)

Figure 1.
Figure 1: Overall comparison of SERCA1a structures representing key states of the reaction cycle. The new structures of Ca[2]E1 P-AMPPN, E2-BeF[3]^- and E2-AlF[4]^- complexes form the basis of this report and the E2-BeF[3]^- complex is increased in size to emphasize its critical importance. Cation- and nucleotide-exchange reactions are indicated. The structures are depicted by grey, transparent surfaces and by cartoon representations, with the A domain in yellow, N domain in red, P domain in blue, transmembrane segment M1–2 in purple, M3–4 in green, M5–6 in wheat and M7–10 in grey. The TGES motif is shown by pink space-filling, residues 309, 771 and 796 (mentioned in the text) as sticks, and bound Ca^2+ ions as grey spheres. Here, and in the following figures, structural representations were prepared with Pymol (http://pymol.sourceforge.net/).

Figure 6.
Figure 6: Schematic representation of the reaction cycle. A schematic selection of key features of Ca^2+-ATPase function is indicated and reveals for the E2-P state the rotation of the A domain dragging M1–2, and the changes in the position of the P domain and N domain, pushing M3–4 in an outward and downward direction. See the Discussion for further detail. A domain, yellow; N domain, red; P domain, blue; helix M1–2, purple; M3–4, green; M5–10, wheat; Ca^2+ ions and protons, green and grey spheres, respectively.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2007, 450, 1036-1042) copyright 2007.

Figures were selected by an automated process.