| http://purl.uniprot.org/citations/16249185 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16249185 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16249185 | http://www.w3.org/2000/01/rdf-schema#comment | "ROCK or Rho-associated kinase, a serine/threonine kinase, is an effector of Rho-dependent signaling and is involved in actin-cytoskeleton assembly and cell motility and contraction. The ROCK protein consists of several domains: an N-terminal region, a kinase catalytic domain, a coiled-coil domain containing a RhoA binding site, and a pleckstrin homology domain. The C-terminal region of ROCK binds to and inhibits the kinase catalytic domains, and this inhibition is reversed by binding RhoA, a small GTPase. Here we present the structure of the N-terminal region and the kinase domain. In our structure, two N-terminal regions interact to form a dimerization domain linking two kinase domains together. This spatial arrangement presents the kinase active sites and regulatory sequences on a common face affording the possibility of both kinases simultaneously interacting with a dimeric inhibitory domain or with a dimeric substrate. The kinase domain adopts a catalytically competent conformation; however, no phosphorylation of active site residues is observed in the structure. We also determined the structures of ROCK bound to four different ATP-competitive small molecule inhibitors (Y-27632, fasudil, hydroxyfasudil, and H-1152P). Each of these compounds binds with reduced affinity to cAMP-dependent kinase (PKA), a highly homologous kinase. Subtle differences exist between the ROCK- and PKA-bound conformations of the inhibitors that suggest that interactions with a single amino acid of the active site (Ala215 in ROCK and Thr183 in PKA) determine the relative selectivity of these compounds. Hydroxyfasudil, a metabolite of fasudil, may be selective for ROCK over PKA through a reversed binding orientation."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m508847200"xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m508847200"xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Jacobs M."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Jacobs M."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Hayakawa K."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Hayakawa K."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Doran J."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Doran J."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Swenson L."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Swenson L."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Bellon S."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Bellon S."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Fleming M."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Fleming M."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Taslimi P."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/author | "Taslimi P."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/pages | "260-268"xsd:string |
| http://purl.uniprot.org/citations/16249185 | http://purl.uniprot.org/core/pages | "260-268"xsd:string |