4i5h

Crystal Structure of a Double Mutant Rat Erk2 Complexed With a Type II Quinazoline InhibitorCrystal Structure of a Double Mutant Rat Erk2 Complexed With a Type II Quinazoline Inhibitor

Structural highlights 4i5h is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Gene: Erk2, Mapk, Mapk1, Prkm1 (Rattus norvegicus) Activity: Mitogen-activated protein kinase, with EC number 2.7.11.24 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Only a small percentage of protein kinases have been shown to adopt a distinct inactive ATP-binding site conformation, called the Asp-Phe-Gly-out (DFG-out) conformation. Given the high degree of homology within this enzyme family, we sought to understand the basis of this disparity on a sequence level. We identified two residue positions that sensitize mitogen-activated protein kinases (MAPKs) to inhibitors that stabilize the DFG-out inactive conformation. After characterizing the structure and dynamics of an inhibitor-sensitive MAPK mutant, we demonstrated the generality of this strategy by sensitizing a kinase (apoptosis signal-regulating kinase 1) not in the MAPK family to several DFG-out stabilizing ligands, using the same residue positions. The use of specific inactive conformations may aid the study of noncatalytic roles of protein kinases, such as binding partner interactions and scaffolding effects. Sequence determinants of a specific inactive protein kinase conformation.,Hari SB, Merritt EA, Maly DJ Chem Biol. 2013 Jun 20;20(6):806-15. doi: 10.1016/j.chembiol.2013.05.005. PMID:23790491 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mitogen-activated protein kinase

spinqualitylabelsall models 4i5h, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image