title: Associations between the Rho kinase-1 catalytic and PH domain regulatory unit.
abstract: Rho-associated kinase, or ROCK, is an important mediator of ventricular remodeling in cardiac hypertrophy. It has a kinase catalytic domain, a coiled-coil domain and a Pleckstrin-Homology domain (PH domain) with a C1 domain insert. The C-terminal region including the PH domain and C1 domain insert is involved in an autoregulatory role for ROCK. We sought to evaluate whether a self association complex could form using computational docking approaches. We found that both the PH domain and the C1 domain could dock with the catalytic domain and we further found that they could dock in poses that are complementary to each other forming a three domain complex. We also confirmed a binding response using a surface plasmon resonance experimental approach. Information about the regulation of ROCK might lead to new strategies to develop lead inhibitor compounds to modulate cardiac remodeling.
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Craft
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Marc N
authors.initials: MN
authors.lastname: Charendoff
authors.forename: Jeffery T
authors.initials: JT
authors.lastname: Mindrebo
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schwartz
authors.forename: James M
authors.initials: JM
authors.lastname: Briggs
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D017124:Conserved Sequence; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D020349:Surface Plasmon Resonance; D054460:rho-Associated Kinases / Q000737:chemistry*
chemical_list: C515851:ROCK1 protein, human; D054460:rho-Associated Kinases
keywords: Docking; PH domain; ROCK; Rho-associated kinase