Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25925954
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2015 ; 290
(25
): 15538-15548
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Phosphoryl Transfer Reaction Snapshots in Crystals: INSIGHTS INTO THE MECHANISM
OF PROTEIN KINASE A CATALYTIC SUBUNIT
#MMPMID25925954
Gerlits O
; Tian J
; Das A
; Langan P
; Heller WT
; Kovalevsky A
J Biol Chem
2015[Jun]; 290
(25
): 15538-15548
PMID25925954
show ga
To study the catalytic mechanism of phosphorylation catalyzed by cAMP-dependent
protein kinase (PKA) a structure of the enzyme-substrate complex representing the
Michaelis complex is of specific interest as it can shed light on the structure
of the transition state. However, all previous crystal structures of the
Michaelis complex mimics of the PKA catalytic subunit (PKAc) were obtained with
either peptide inhibitors or ATP analogs. Here we utilized Ca(2+) ions and sulfur
in place of the nucleophilic oxygen in a 20-residue pseudo-substrate peptide
(CP20) and ATP to produce a close mimic of the Michaelis complex. In the ternary
reactant complex, the thiol group of Cys-21 of the peptide is facing Asp-166 and
the sulfur atom is positioned for an in-line phosphoryl transfer. Replacement of
Ca(2+) cations with Mg(2+) ions resulted in a complex with trapped products of
ATP hydrolysis: phosphate ion and ADP. The present structural results in
combination with the previously reported structures of the transition state mimic
and phosphorylated product complexes complete the snapshots of the phosphoryl
transfer reaction by PKAc, providing us with the most thorough picture of the
catalytic mechanism to date.