Kinetic mechanism and ATP-binding site reactivity of p38γ MAP kinase

被引：29

作者：

Fox, T ^{[1
]}

Fitzgibbon, MJ ^{[1
]}

Fleming, MA ^{[1
]}

Hsiao, HM ^{[1
]}

Brummel, CL ^{[1
]}

Su, MSS ^{[1
]}

机构：

[1] Vertex Pharmaceut Inc, Cambridge, MA 02139 USA

来源：

FEBS LETTERS | 1999年 / 461卷 / 03期

关键词：

MAP kinase; p38; gamma; kinetic mechanism; ATPase; ATP-binding site; kinase; 5 '-(p-fluorosulfonylbenzoyl)adenosine;

D O I：

10.1016/S0014-5793(99)01488-X

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Activated p38 gamma MAP kinase exhibited significant basal ATPase activity in the absence of a kinase substrate, and addition of a phosphoacceptor substrate increased k(cat)/K-m > 20-fold. AMP-PCP was competitive with ATP binding and noncompetitive with phosphoacceptor substrate binding. The nucleotide binding site affinity label 5'-(p-fluorosulfonylbenzoyl)adenosine (FSBA) bound stoichiometrically at Lys-56 in the ATP site of both unphosphorylated and activated p38 gamma, AMP-PCP only protected the activated enzyme from FSBA inactivation, implying that AMP-PCP does not bind unphosphorylated p38 gamma. Basal ATPase activities were also observed for activated p38 alpha, ERK2 and JNK3 suggesting that the enzymatic mechanism may be similar for all classes of MAP kinases, (C) 1999 Federation of European Biochemical Societies.

引用

页码：323 / 328

页数：6

共 32 条

[1] The structure of phosphorylated P38γ is monomeric and reveals a conserved activation-loop conformation [J].