2mtq

Solution Structure of a De Novo Designed Peptide that Sequesters Toxic Heavy Metals

spinqualitylabelsall models 2mtq Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2mtq is a 1 chain structure with sequence from Escherichia coli BL21(DE3). Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed De novo protein design is a biologically relevant approach that provides a novel process in elucidating protein folding and modeling the metal centers of metalloproteins in a completely unrelated or simplified fold. An integral step in de novo protein design is the establishment of a well-folded scaffold with one conformation, which is a fundamental characteristic of many native proteins. Here, we report the NMR solution structure of apo alpha3DIV at pH 7.0, a de novo designed three-helix bundle peptide containing a triscysteine motif (Cys18, Cys28, and Cys67) that binds toxic heavy metals. The structure comprises 1067 NOE restraints derived from multinuclear multidimensional NOESY experiments, as well as 168 dihedral angles (psi, phi and chi1). The backbone and heavy atoms of the 20 lowest energy structures have an RMSD from the mean structure of 0.79 (0.16) A and 1.31 (0.15) A, respectively. When compared to the parent structure alpha3D, the substitution of Leu residues to Cys enhanced the alpha-helical content of alpha3DIV while maintaining the same overall topology and fold. In addition, solution studies on the metallated species illustrated metal-induced stability. An increase in the melting temperatures was observed for Hg(II), Pb(II) or Cd(II) bound alpha3DIV by 18 - 24 degrees C compared to its apo counterpart. Further, the EXAFS analysis on Hg(II)-alpha3DIV produced an average Hg(II)-S bond length at 2.36 A, indicating a trigonal T-shaped coordination environment. Overall, the structure of apo alpha3DIV reveals an asymmetric distorted triscysteine metal binding site, which offers a model for native metalloregulatory proteins with thiol-rich ligands that function in regulating toxic heavy metals, such as ArsR, CadC, MerR, and PbrR. Apoprotein Structure and Metal Binding Characterization of a De Novo Designed Peptide, alphaDIV, that Sequesters Toxic Heavy Metals.,Plegaria JS, Dzul S, Zuiderweg ER, Stemmler TL, Pecoraro VL Biochemistry. 2015 Mar 19. PMID:25790102 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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