4iww

Computational Design of an Unnatural Amino Acid Metalloprotein with Atomic Level Accuracy

spinqualitylabelsall models 4iww, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4iww is a 2 chain structure with sequence from Saccharolobus solfataricus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: BP5, CO, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRPC_SACS2 Publication Abstract from PubMed Genetically encoded unnatural amino acids could facilitate the design of proteins and enzymes of novel function, but correctly specifying sites of incorporation, and the identities and orientations of surrounding residues represents a formidable challenge. Computational design methods have been used to identify optimal locations for functional sites in proteins and design the surrounding residues, but have not incorporated unnatural amino acids in this process. We extended the Rosetta design methodology to design metalloproteins in which the amino acid (2,2'-bipyridin-5yl)alanine (Bpy-Ala) is a primary ligand of a bound metal ion. Following initial results that indicated the im-portance of buttressing the Bpy-Ala amino acid, we designed a buried metal binding site with octahedral coordination geometry consisting of Bpy-Ala, two protein based metal ligands, and two metal bound water molecules. Experimental characterization revealed a Bpy-Ala mediated metalloprotein with the ability to bind divalent cations including Co2+, Zn2+, Fe2+, and Ni2+, with a Kd for Zn2+ of ~40 pM. X-ray crystallograph-ic analysis of the designed protein shows only slight deviation from the computationally designed model. Computational Design of an Unnatural Amino Acid Dependent Metalloprotein with Atomic Level Accuracy.,Mills JH, Khare SD, Bolduc JM, Forouhar F, Mulligan VK, Lew S, Seetharaman J, Tong L, Stoddard BL, Baker D J Am Chem Soc. 2013 Aug 7. PMID:23924187 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also IGPS 3D structures

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