Sulfate Acts as Phosphate Analog on the Monomeric Catalytic Fragment of the CPx-ATPase CopB from Sulfolobus solfataricus

Lübben, Mathias; Güldenhaupt, Jörn; Zoltner, Martin; Deigweiher, Katrin; Haebel, Peter; Urbanke, Claus; Scheidig, Axel J.

doi:10.1016/j.jmb.2007.03.029

Cited by 22 publications

(38 citation statements)

References 68 publications

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“…However, several X-ray and NMR studies have been successfully used to solve the structures of the three cytoplasmatic soluble domains of copper(I)-transporting ATPases, A-, Pand N-domains, from bacteria and human, both as isolated domains (i.e., A-domain [64,65] and N-domain [66,67]), and as composite N-and P-domains [68][69][70]; also NMR studies have provided structures of various isolated or double-domain constructs of NMBDs in different metallation states [71][72][73][74][75].…”

Section: Copper Import Into the Cytoplasmmentioning

confidence: 99%

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Cellular copper distribution: a mechanistic systems biology approach

Banci

Bertini

Cantini

et al. 2010

Cell. Mol. Life Sci.

156

120

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Copper is an essential but potentially harmful trace element required in many enzymatic processes involving redox chemistry. Cellular copper homeostasis in mammals is predominantly maintained by regulating copper transport through the copper import CTR proteins and the copper exporters ATP7A and ATP7B. Once copper is imported into the cell, several pathways involving a number of copper proteins are responsible for trafficking it specifically where it is required for cellular life, thus avoiding the release of harmful free copper ions. In this study we review recent progress made in understanding the molecular mechanisms of copper transport in cells by analyzing structural features of copper proteins, their mode of interaction, and their thermodynamic and kinetic parameters, thus contributing to systems biology of copper within the cell.

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Section: Copper Import Into the Cytoplasmmentioning

confidence: 99%

“…2) [68][69][70]. The structures of the entire bacterial ATP-binding domain and those of the human isolated N-domain reveal that the latter consists of a twisted six-stranded, antiparallel b-sheet, flanked by two pairs of a-helices, one on the concave side of the sheet and the other on the convex one.…”

Section: Copper Import Into the Cytoplasmmentioning

confidence: 99%

Cellular copper distribution: a mechanistic systems biology approach

Banci

Bertini

Cantini

et al. 2010

Cell. Mol. Life Sci.

156

120

View full text Add to dashboard Cite

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“…13). However, the consensus sequence for the TGES signature (A domain) is specifically limited to the transport ATPases, and does not include the phosphoserine phosphatase, as also demonstrated by structural studies (46,47). This homology is related to the specific and prominent role sustained by the A ("actuator") domain in the catalytic and transport mechanism of P ATPases, as the A domain lends itself to rotation and bending.…”

Section: Preparation Of T Maritimamentioning

confidence: 99%

Intermediate Phosphorylation Reactions in the Mechanism of ATP Utilization by the Copper ATPase (CopA) of Thermotoga maritima

Hatori

Hirata

Toyoshima

et al. 2008

Journal of Biological Chemistry

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Recombinant and purified Thermotoga maritima CopA sustains ATPase velocity of 1.78 -2.73 mol/mg/min in the presence of Cu ؉ (pH 6, 60°C) and 0.03-0.08 mol/mg/min in the absence of Cu ؉ . High levels of enzyme phosphorylation are obtained by utilization of [␥-32 P]ATP in the absence of Cu ؉ . This phosphoenzyme decays at a much slower rate than observed with Cu⅐E1 ϳ P. In fact, the phosphoenzyme is reduced to much lower steady state levels upon addition of Cu ؉ , due to rapid hydrolytic cleavage. Negligible ATPase turnover is sustained by CopA following deletion of its N-metal binding domain (⌬NMBD) or mutation of NMBD cysteines (CXXC). Nevertheless, high levels of phosphoenzyme are obtained by utilization of [␥-32 P]ATP by the ⌬NMBD and CXXC mutants, with no effect of Cu ؉ either on its formation or hydrolytic cleavage. Phosphoenzyme formation (E2P) can also be obtained by utilization of P i , and this reaction is inhibited by Cu ؉ (E2 to E1 transition) even in the ⌬NMBD mutant, evidently due to Cu ؉ binding at a (transport) site other than the NMBD. E2P undergoes hydrolytic cleavage faster in ⌬NMBD and slower in CXXC mutant. We propose that Cu ؉ binding to the NMBD is required to produce an "active" conformation of CopA, whereby additional Cu ؉ bound to an alternate (transmembrane transport) site initiates faster cycles including formation of Cu⅐E1 ϳ P, followed by the E1 ϳ P to E2-P conformational transition and hydrolytic cleavage of phosphate. An H479Q mutation (analogous to one found in Wilson disease) renders CopA unable to utilize ATP, whereas phosphorylation by P i is retained.Cation transport ATPases utilize ATP-free energy for transport of specific ions across biological membranes, against electrochemical gradients. They are referred to as P-type ATPases when enzyme phosphorylation, obtained by phosphoryl transfer from ATP to the enzyme protein, is an obligatory intermediate step in the mechanism of ATP utilization and coupled cation transport (1-3). The P-type ATPase family is divided into five branches referred to as I-V (4), including the important PII-type ATPases, which are specific for H , and Co 2ϩ (5). The PIB ATPases sustain important roles in accumulation and tolerance of heavy metal in biological systems (6 -8), as well as for delivery of copper to metalloenzymes (9). Two ATPases of this subgroup serve as copper transporters in humans (10). Mutations of these proteins are involved in the etiology of Menkes and Wilson diseases (8,(11)(12)(13). The catalytic mechanism of the PIB ATPases has been the subject of preliminary studies (14 -19).For a comparative evaluation, it is useful to consider that the structure of PII-type ATPases, originally established for the Ca 2ϩ -ATPase by sequence analysis (20) and crystallography (21), includes three cytosolic domains referred to as N (nucleotide binding), P (phosphorylation), and A (actuator) domains, and 10 transmembrane helices containing the specific cation binding site for catalytic activation and transport. On the other hand, the structure of the...

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“…Interestingly, these domains exhibit the same structure as the small chaperones which route copper intracellularly, like CopZ of E. hirae, Atx1 of Saccharomyces cerevisiae, or human Hah1 (Wimmer et al 1999;Rosenzweig et al 1999;Wernimont et al 2000). The structures of the A-domain of the CopA copper ATPase of the thermophile Archaeoglobus fulgidus (Sazinsky et al 2006a) as well as the combined PN-domains of A. fulgidus (Sazinsky et al 2006b) and Sulfolobus solfataricus (Lübben et al 2007) have also recently been solved. The lack of a complete structure of a heavy metal ATPase has prompted us to investigate the topology of the CopA copper ATPase of E. hirae by chemical cross-linking.…”

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confidence: 99%

Structural model of the CopA copper ATPase of Enterococcus hirae based on chemical cross-linking

et al. 2008

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The CopA copper ATPase of Enterococcus hirae belongs to the family of heavy metal pumping CPx-type ATPases and shares 43% sequence similarity with the human Menkes and Wilson copper ATPases. Due to a lack of suitable protein crystals, only partial three-dimensional structures have so far been obtained for this family of ion pumps. We present a structural model of CopA derived by combining topological information obtained by intramolecular cross-linking with molecular modeling. Purified CopA was crosslinked with different bivalent reagents, followed by tryptic digestion and identification of cross-linked peptides by mass spectrometry. The structural proximity of tryptic fragments provided information about the structural arrangement of the hydrophilic protein domains, which was integrated into a three-dimensional model of CopA. Comparative modeling of CopA was guided by the sequence similarity to the calcium ATPase of the sarcoplasmic reticulum, Serca1, for which detailed structures are available. In addition, known partial structures of CPx-ATPase homologous to CopA were used as modeling templates. A docking approach was used to predict the orientation of the heavy metal binding domain of CopA relative to the core structure, which was verified by distance constraints derived from cross-links. The overall structural model of CopA resembles the Serca1 structure, but reveals distinctive features of CPx-type ATPases. A prominent feature is the positioning of the heavy metal binding domain. It features an orientation of the Cu binding ligands which is appropriate for the interaction with Cu-loaded metallochaperones in solution. Moreover, a novel model of the architecture of the intramembranous Cu binding sites could be derived.

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Sulfate Acts as Phosphate Analog on the Monomeric Catalytic Fragment of the CPx-ATPase CopB from Sulfolobus solfataricus

Cited by 22 publications

References 68 publications

Cellular copper distribution: a mechanistic systems biology approach

Cellular copper distribution: a mechanistic systems biology approach

Intermediate Phosphorylation Reactions in the Mechanism of ATP Utilization by the Copper ATPase (CopA) of Thermotoga maritima

Structural model of the CopA copper ATPase of Enterococcus hirae based on chemical cross-linking

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