TY  - JOUR
A1  - Barth, Andreas
A1  - Bezlyepkina, Natalya
T1  - P-O bond destabilization accelerates phosphoenzyme hydrolysis of sarcoplasmic reticulum Ca2+-ATPase
T2  - Journal of biological chemistry
N2  - The phosphate group of the ADP-insensitive phosphoenzyme (E2-P) of sarcoplasmic reticulum Ca2+-ATPase (SERCA1a) was studied with infrared spectroscopy to understand the high hydrolysis rate of E2-P. By monitoring an autocatalyzed isotope exchange reaction, three stretching vibrations of the transiently bound phosphate group were selectively observed against a background of 50,000 protein vibrations. They were found at 1194, 1137, and 1115 cm–1. This information was evaluated using the bond valence model and empirical correlations. Compared with the model compound acetyl phosphate, structure and charge distribution of the E2-P aspartyl phosphate resemble somewhat the transition state in a dissociative phosphate transfer reaction; the aspartyl phosphate of E2-P has 0.02 Å shorter terminal P–O bonds and a 0.09 Å longer bridging P–O bond that is ∼20% weaker, the angle between the terminal P–O bonds is wider, and –0.2 formal charges are shifted from the phosphate group to the aspartyl moiety. The weaker bridging P–O bond of E2-P accounts for a 1011–1015-fold hydrolysis rate enhancement, implying that P–O bond destabilization facilitates phosphoenzyme hydrolysis. P–O bond destabilization is caused by a shift of noncovalent interactions from the phosphate oxygens to the aspartyl oxygens. We suggest that the relative positioning of Mg2+ and Lys684 between phosphate and aspartyl oxygens controls the hydrolysis rate of the ATPase phosphoenzymes and related phosphoproteins.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76166
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-761668
SN  - 0021-9258
VL  - 279
IS  - 50
SP  - 51888
EP  - 51896
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -