5OD1

Structure of the engineered metalloesterase MID1sc10 complexed with a phosphonate transition state analogue

Summary for 5OD1

• Entry DOI: 10.2210/pdb5od1/pdb
• Descriptor: MID1sc10, ZINC ION, [2-oxidanylidene-7-[oxidanyl-[(1~{S})-1-phenylethyl]phosphoryl]oxy-chromen-4-yl]methanesulfonic acid, ... (5 entities in total)
• Functional Keywords: directed evolution, engineered metalloenzyme, de novo protein-hydrolase, de novo protein-hydrolase complex, de novo protein/hydrolase
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 11450.94

Authors

Mittl, P.R.E.,Studer, S.,Hansen, D.A.,Hilvert, D. (deposition date: 2017-07-04, release date: 2018-12-12, Last modification date: 2024-05-08)

Primary citation

Studer, S.,Hansen, D.A.,Pianowski, Z.L.,Mittl, P.R.E.,Debon, A.,Guffy, S.L.,Der, B.S.,Kuhlman, B.,Hilvert, D.
Evolution of a highly active and enantiospecific metalloenzyme from short peptides.
Science, 362:1285-1288, 2018

PubMed Abstract: Primordial sequence signatures in modern proteins imply ancestral origins tracing back to simple peptides. Although short peptides seldom adopt unique folds, metal ions might have templated their assembly into higher-order structures in early evolution and imparted useful chemical reactivity. Recapitulating such a biogenetic scenario, we have combined design and laboratory evolution to transform a zinc-binding peptide into a globular enzyme capable of accelerating ester cleavage with exacting enantiospecificity and high catalytic efficiency ( / ~ 10 M s). The simultaneous optimization of structure and function in a naïve peptide scaffold not only illustrates a plausible enzyme evolutionary pathway from the distant past to the present but also proffers exciting future opportunities for enzyme design and engineering.

PubMed: 30545884
DOI: 10.1126/science.aau3744

Experimental method

X-RAY DIFFRACTION (1.34 Å)