This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2erz
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 2erz |SIZE=350|CAPTION= <scene name='initialview01'>2erz</scene>, resolution 2.200Å | |PDB= 2erz |SIZE=350|CAPTION= <scene name='initialview01'>2erz</scene>, resolution 2.200Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=HFS:1-(1-HYDROXY-5-ISOQUINOLINESULFONYL)HOMOPIPERAZINE'>HFS</scene> | + | |LIGAND= <scene name='pdbligand=HFS:1-(1-HYDROXY-5-ISOQUINOLINESULFONYL)HOMOPIPERAZINE'>HFS</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span> |
|GENE= Prkaca, Pkaca ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]) | |GENE= Prkaca, Pkaca ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2esm|2ESM]], [[2etr|2ETR]], [[2eto|2ETO]], [[2etk|2ETK]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2erz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2erz OCA], [http://www.ebi.ac.uk/pdbsum/2erz PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2erz RCSB]</span> | ||
}} | }} | ||
| Line 24: | Line 27: | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Jacobs, M.]] | [[Category: Jacobs, M.]] | ||
| - | [[Category: HFS]] | ||
[[Category: fasudil kinase]] | [[Category: fasudil kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:53:00 2008'' |
Revision as of 23:53, 30 March 2008
| |||||||
| , resolution 2.200Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | Prkaca, Pkaca (Mus musculus) | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Related: | 2ESM, 2ETR, 2ETO, 2ETK
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of c-AMP Dependent Kinase (PKA) bound to hydroxyfasudil
Overview
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.
About this Structure
2ERZ is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
The structure of dimeric ROCK I reveals the mechanism for ligand selectivity., Jacobs M, Hayakawa K, Swenson L, Bellon S, Fleming M, Taslimi P, Doran J, J Biol Chem. 2006 Jan 6;281(1):260-8. Epub 2005 Oct 24. PMID:16249185
Page seeded by OCA on Mon Mar 31 02:53:00 2008
