Chemistry and energetics of transphosphorylations in the mechanism of Na+/K+-transporting ATPase: an attempt at a unifying model

Repke, K.; R, Schön

doi:10.1016/0304-4157(93)90014-f

Cited by 7 publications

(1 citation statement)

References 93 publications

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“…K ϩ ions, which greatly accelerate hydrolysis, act at a distance, and a likely mechanism involves induction of an appropriate configuration for ''in-line'' nucleophilic attack by water on the phosphorus. Repke and Schon have proposed that pseudorotation about the COOOP bonds is necessary to labilize the OOP bond to water (33). This mechanism also implies a change in geometry of the phosphate ligands.…”

Section: Consequences Of Domain Movementsmentioning

confidence: 99%

The complex ATP–Fe ²⁺ serves as a specific affinity cleavage reagent in ATP-Mg ²⁺ sites of Na,K-ATPase: Altered ligation of Fe ²⁺ (Mg ²⁺ ) ions accompanies the E ₁ P→E ₂ P conformational change

Patchornik

Goldshleger

Karlish

2000

Proc. Natl. Acad. Sci. U.S.A.

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In the presence of ascorbate͞H2O2, ATP-Fe 2؉ or AMP-PNP-Fe 2؉ complexes act as affinity cleavage reagents, mediating selective cleavage of the alpha subunit of Na,K-ATPase at high affinity ATP-Mg 2؉ sites. The cleavages reveal contact points of Fe 2؉ or Mg 2؉ ions. In E1 and E 1Na conformations, two major cleavages are detected within the conserved 708 TGDGVNDSPALKK sequence (at V712 and nearby), and one (E1Na) or two (E1) minor cleavages near V440. In media containing sodium and ATP, Fe 2؉ A long series of experiments established the Post-Albers kinetic mechanism of Na,K-ATPase and related P-type cation pumps (1-3). Active Na ϩ and K ϩ transport involves (i) Na cyt -dependent phosphorylation from ATP, and Na ϩ occlusion, E 1 3E 1 P(Na); (ii) Na ϩ transport outward across the membrane coupled to E 1 P3E 2 P; (iii) K exc -activated dephosphorylation, and occlusion, E 2 P3E 2 (K); and (iv) K ϩ transport inward across the membrane coupled to E 2 (K)3E 1 , accelerated by ATP acting with low affinity. For other pumps, steps i or iii are activated by the appropriate cations, which are transported in steps ii or iv.Despite our extensive knowledge of function, a proper understanding of active transport cannot be achieved without knowledge of molecular structure. In this regard, the recent publication of the 2.6-Å crystal structure of sarcoplasmic reticulum Ca-ATPase is an event of unparalleled importance (4). The structure confirms the existence of ten transmembrane helices deduced for Ca, Na,K Ϫ , H,K Ϫ , and H-pumps by biochemical techniques (5) and reveals several unexpected features, including distortion of the M4 and M6 membrane-spanning helices involved in occluding Ca ions. The details of Ca occlusion sites fit well with those deduced in extensive mutagenesis studies (3, 6). The cytoplasmic sector of the pump is divided into three domains, two domains N (nucleotide) and P (phosphorylation) within the loop between M4 and M5, well separated from a third A (actuator or anchor) domain containing the loop between M2 and M3 and the segment leading into M1. The fold of the P domain is like that of haloacid dehydogenase and related proteins with homologies to P-type pumps in conserved cytoplasmic sequences (7,8). Comparison of the crystal structure (an E 1 ⅐Ca conformation) with cryoelectron microscope images of Ca-ATPase in both E 1 or E 2 conformations (9), suggested that, in the change from E 1 to E 2 , domain A makes contact with the P͞N domain (see below). Presumably, the tertiary structures of other P-type pumps will resemble that of Ca-ATPase, particularly within the cytoplasmic domains, but will show detailed differences related to the cation specificities, and for Na,K-ATPase and H,K-ATPase to the presence of a ␤ subunit .Important as it is, the crystal structure of a pump in one conformation cannot provide full structural information on other conformations. Recently, we described a technique of specific oxidative cleavage of renal Na,K-ATPase, which utilizes Fe 2ϩ ͞ascorbate͞H 2 O 2 and provides unique inform...

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Section: Consequences Of Domain Movementsmentioning

confidence: 99%

The complex ATP–Fe ²⁺ serves as a specific affinity cleavage reagent in ATP-Mg ²⁺ sites of Na,K-ATPase: Altered ligation of Fe ²⁺ (Mg ²⁺ ) ions accompanies the E ₁ P→E ₂ P conformational change

Patchornik

Goldshleger

Karlish

2000

Proc. Natl. Acad. Sci. U.S.A.

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Reinstatement of the ATP high energy paradigm

Repke

1996

Biochemical Mechanisms in Heart Function

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Katalyse und Regulation bioenergetischer Prozesse durch die Erdalkalimetallionen Mg2+ und Ca2+

Kaim

Schwederski

1995

Teubner Studienbücher Chemie

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Chemistry and energetics of transphosphorylations in the mechanism of Na+/K+-transporting ATPase: an attempt at a unifying model

Cited by 7 publications

References 93 publications

The complex ATP–Fe ²⁺ serves as a specific affinity cleavage reagent in ATP-Mg ²⁺ sites of Na,K-ATPase: Altered ligation of Fe ²⁺ (Mg ²⁺ ) ions accompanies the E ₁ P→E ₂ P conformational change

The complex ATP–Fe ²⁺ serves as a specific affinity cleavage reagent in ATP-Mg ²⁺ sites of Na,K-ATPase: Altered ligation of Fe ²⁺ (Mg ²⁺ ) ions accompanies the E ₁ P→E ₂ P conformational change

Reinstatement of the ATP high energy paradigm

Katalyse und Regulation bioenergetischer Prozesse durch die Erdalkalimetallionen Mg2+ und Ca2+

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Chemistry and energetics of transphosphorylations in the mechanism of Na+/K+-transporting ATPase: an attempt at a unifying model

Cited by 7 publications

References 93 publications

The complex ATP–Fe 2+ serves as a specific affinity cleavage reagent in ATP-Mg 2+ sites of Na,K-ATPase: Altered ligation of Fe 2+ (Mg 2+ ) ions accompanies the E 1 P→E 2 P conformational change

The complex ATP–Fe 2+ serves as a specific affinity cleavage reagent in ATP-Mg 2+ sites of Na,K-ATPase: Altered ligation of Fe 2+ (Mg 2+ ) ions accompanies the E 1 P→E 2 P conformational change

Reinstatement of the ATP high energy paradigm

Katalyse und Regulation bioenergetischer Prozesse durch die Erdalkalimetallionen Mg2+ und Ca2+

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Product

Resources

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The complex ATP–Fe ²⁺ serves as a specific affinity cleavage reagent in ATP-Mg ²⁺ sites of Na,K-ATPase: Altered ligation of Fe ²⁺ (Mg ²⁺ ) ions accompanies the E ₁ P→E ₂ P conformational change

The complex ATP–Fe ²⁺ serves as a specific affinity cleavage reagent in ATP-Mg ²⁺ sites of Na,K-ATPase: Altered ligation of Fe ²⁺ (Mg ²⁺ ) ions accompanies the E ₁ P→E ₂ P conformational change