########     ###    ##    ## ########  ######  
##     ##   ## ##   ###   ##    ##    ##    ## 
##     ##  ##   ##  ####  ##    ##    ##       
########  ##     ## ## ## ##    ##     ######  
##        ######### ##  ####    ##          ## 
##        ##     ## ##   ###    ##    ##    ## 
##        ##     ## ##    ##    ##     ######  

PETase ANnotation and Triage System

Nature's solution to a human-made health problem

FAST-PETase

290 aa · engineered from IsPETase · Lu et al. 2022, Nature (MutCompute)

38x activity over ThermoPETase, its scaffold; 33.8 mM monomers in 96 h

Structure, superposed on IsPETase

Aligned onto IsPETase 6EQE when it was written, so anything added below overlays directly and the browser does no alignment. The catalytic triad is drawn from the residues the geometry stage measured, not from positions inferred by an alignment.

Overlay another

Sequence 290 aa · 5 substitutions

catalytic triad   substitution against IsPETase  · the same colours as the viewer above. Triad positions are labelled; hover any residue for its number. Click one to select it in both.

MNFPRASRLMQAAVLGGLMAVSAAATAQTNPYARGPNPTAASLEASAGPFTVRSFTVSRPSGYGAGTVYYPTNAGGTVGAIAIVPGYTARQSSIKWWGPRLASHGFVVITIDTNSTLDQPESRSSQQMAALRQVASLNGTSSSPIYGKVDTARMGVMGW160SMGGGGSLISAANNPSLKAAAPQAPWHSSTNFSSVTVPTLIFACEN206DSIAPVNSSALPIYDSMSQNAKQFLEIKGGS237HSCANSGNSNQALIGKKGVAWMKRFMDNDTRYSTFACENPNSTAVSDFRTANCS

Activity

Optimum temperature50.0 °C
As publishedOptimum temperature 50 degC. 38x activity over IsPETase; 33.8 mM monomers in 96 h. Primary reference: Lu et al. 2022, Nature. Value taken from a secondary review, NOT from the primary paper and NOT carrying an ECO evidence code: weaker provenance than the UniProt-extracted rows.
Optimum pHnot recorded
Familypetase_like

Structure

Source Experimental, PDB 7SH6
Resolution1.44 Å
Residues261
Cα RMSD to IsPETase0.13 Å

Active site

Catalytic triadSer160 · His237 · Asp206
Ser OG → His NE22.85 Å
His ND1 → Asp OD3.01 Å
Oxyanion donor 1161 (3.32 Å)
Oxyanion donor 287 (5.61 Å)
Cleft width22.16 Å
Cleft depth4.32 Å
Cleft residues84

Aromatic clamp: PHE201 · TRP159 · TRP185 · TYR219 · TYR87

Mutations

S121E, D186H, R224Q, N233K, R280A

5 substitutions against IsPETase. Every one was applied by a routine that refuses any substitution whose stated parent residue does not match, so a wrong position or a mature-versus-precursor numbering shift fails loudly rather than producing a plausible but wrong sequence.

ThermoPETase scaffold plus R224Q/N233K. Machine-learning designed. HAS an experimental structure, contrary to a first look: 7SH6 appears to carry 19 substitutions against IsPETase, but 14 of those are a heterologous secretion leader replacing the native signal peptide, and its MATURE chain (residue 28 on) is identical to FAST-PETase. 8J45 is the same protein again, expressed in Pichia pastoris, differing only by an EF cloning scar where the mature sequence begins QT. Comparing whole precursors instead of mature chains is what hid this.

Reference: Lu et al. 2022, Nature (MutCompute) doi:10.1038/s41586-022-04599-z

Measured activity

ParameterValueSubstrateEvidenceSource
performance claim PET from review 10.1038/s41586-022-04599-z
38x activity over ThermoPETase, its scaffold; 33.8 mM monomers in 96 h
topt 50.0 degC PET from review 10.1038/s41586-022-04599-z
Optimum temperature 50 degC. 38x activity over IsPETase; 33.8 mM monomers in 96 h. Primary reference: Lu et al. 2022, Nature. Value taken from a secondary review, NOT from the primary paper and NOT carrying an ECO evidence code: weaker provenance than the UniProt-extracted rows.

Related in PANTS

Lineage

Engineered from IsPETase.

Nearest metagenomic candidates

No candidate in the catalogue names this enzyme as its nearest match.

Identifiers and cross-references

ThermoPETase scaffold plus R224Q/N233K. Machine-learning designed. HAS an experimental structure, contrary to a first look: 7SH6 appears to carry 19 substitutions against IsPETase, but 14 of those are a heterologous secretion leader replacing the native signal peptide, and its MATURE chain (residue 28 on) is identical to FAST-PETase. 8J45 is the same protein again, expressed in Pichia pastoris, differing only by an EF cloning scar where the mature sequence begins QT. Comparing whole precursors instead of mature chains is what hid this.