4ehk | pdb_00004ehk

Allosteric Modulation of Caspase-3 through Mutagenesis

spinqualitylabelsall models 4ehk, resolution 1.67Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ehk is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: 0QE, ACE Related: 4eha, 4ehd, 4ehf, 4ehh, 4ehl, 4ehn Gene: CASP3, CPP32 (Homo sapiens) Activity: Caspase-3, with EC number 3.4.22.56 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed A mutation in the allosteric site of the caspase-3 dimer interface of V266 to histidine abolishes activity of the enzyme, and models predict that the mutation mimics the action of small molecule allosteric inhibitors by preventing formation of the active site. Mutations were coupled to H266 at two sites in the interface, E124A and Y197C. We present data from X-ray crystallography, enzymatic activity and molecular dynamics simulations for seven proteins, consisting of single, double, and triple mutants. The data demonstrate that considering allosteric inhibition of caspase-3 as a shift between discrete "off-state" or "on-state" conformations is insufficient. While H266 is accommodated in the interface, the structural defects are propagated to the active site through a helix on the protein surface. A more comprehensive view of allosteric regulation of caspase-3 requires the representation of an ensemble of inactive states and shows that subtle structural changes lead to the population of the inactive ensemble. Allosteric Modulation of Caspase-3 through Mutagenesis.,Walters J, Schipper JL, Swartz P, Mattos C, Clark AC Biosci Rep. 2012 May 18. PMID:22607239 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Caspase

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