1997
DOI: 10.1038/nsb0497-311
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A highly specific inhibitor of human p38 MAP kinase binds in the ATP pocket

Abstract: The crystal structure of human p38 mitogen-activated protein (MAP) kinase in complex with a potent and highly specific pyridinyl-imidazole inhibitor has been determined at 2.0 A resolution. The structure of the kinase, which is in its unphosphorylated state, is similar to that of the closely-related ERK2. The inhibitor molecule is bound in the ATP pocket. A hydrogen bond is made between the pyridyl nitrogen of the inhibitor and the main chain amido nitrogen of residue 109, analogous to the interaction from the… Show more

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Cited by 389 publications
(325 citation statements)
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“…6C). To assess whether P38 was the mediator of stretchinduced HSP27 phosphorylation, podocytes were exposed to stretch for 10 min either in the presence or in the absence of SB202190 (1 M), a compound that specifically inhibits P38 by binding to its ATP pocket (35). We found that the addition of SB202190 completely abolished stretch-induced HSP27 phosphorylation at 10 min (Fig.…”
Section: P38 Mapk Mediates Stretch-induced Hsp27 Phosphorylationmentioning
confidence: 79%
“…6C). To assess whether P38 was the mediator of stretchinduced HSP27 phosphorylation, podocytes were exposed to stretch for 10 min either in the presence or in the absence of SB202190 (1 M), a compound that specifically inhibits P38 by binding to its ATP pocket (35). We found that the addition of SB202190 completely abolished stretch-induced HSP27 phosphorylation at 10 min (Fig.…”
Section: P38 Mapk Mediates Stretch-induced Hsp27 Phosphorylationmentioning
confidence: 79%
“…Phosphorylation of p38 MAP kinases could also be modulated through direct interaction of the inhibitor with the enzyme as indicated by the identiÂźcation of a possible second binding site outside the ATP pocket with currently unknown function (Tong et al, 1998). More experiments will be necessary to test these possibilities.…”
Section: Discussionmentioning
confidence: 99%
“…SB 203580 binds competitively with ATP (Young et al, 1997) and the three-dimensional structure of SAPK2a/p38a in a complex with closely related pyridinyl imidazoles has established that these drugs are inserted into the ATP-binding pocket of SAPK2a/ p38a (Tong et al, 1997;Wilson et al, 1997). However, the 4-ÂŻuorophenyl ring of the drug does not make contact with residues in the ATP-binding pocket that interact with ATP.…”
Section: Introductionmentioning
confidence: 99%