6MCD

Crystal Structure of tris-thiolate Pb(II) complex with adjacent water in a de novo Three Stranded Coiled Coil Peptide

Summary for 6MCD

• Entry DOI: 10.2210/pdb6mcd/pdb
• Related: 6EGF
• Descriptor: Pb(II)(GRAND Coil Ser L12CL16A)-, LEAD (II) ION, ZINC ION, ... (4 entities in total)
• Functional Keywords: metallopeptide de novo design, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 4369.37

Authors

Tolbert, A.E.,Ruckthong, L.,Stuckey, J.A.,Pecoraro, V.L. (deposition date: 2018-08-31, release date: 2020-03-04, Last modification date: 2024-11-20)

Primary citation

Tolbert, A.E.,Ervin, C.S.,Ruckthong, L.,Paul, T.J.,Jayasinghe-Arachchige, V.M.,Neupane, K.P.,Stuckey, J.A.,Prabhakar, R.,Pecoraro, V.L.
Heteromeric three-stranded coiled coils designed using a Pb(II)(Cys)3template mediated strategy.
Nat.Chem., 12:405-411, 2020

PubMed Abstract: Three-stranded coiled coils are peptide structures constructed from amphipathic heptad repeats. Here we show that it is possible to form pure heterotrimeric three-stranded coiled coils by combining three distinct characteristics: (1) a cysteine sulfur layer for metal coordination, (2) a thiophilic, trigonal pyramidal metalloid (Pb(II)) that binds to these sulfurs and (3) an adjacent layer of reduced steric bulk generating a cavity where water can hydrogen bond to the cysteine sulfur atoms. Cysteine substitution in an a site yields Pb(II)AB heterotrimers, while d sites provide pure Pb(II)CD or Pb(II)CD scaffolds. Altering the metal from Pb(II) to Hg(II) or shifting the relative position of the sterically less demanding layer removes heterotrimer specificity. Because only two of the eight or ten hydrophobic layers are perturbed, catalytic sites can be introduced at other regions of the scaffold. A Zn(II)(histidine)(HO) centre can be incorporated at a remote location without perturbing the heterotrimer selectivity, suggesting a unique strategy to prepare dissymmetric catalytic sites within self-assembling de novo-designed proteins.

PubMed: 32123337
DOI: 10.1038/s41557-020-0423-6

Experimental method

X-RAY DIFFRACTION (1.5 Å)