7QC9

HisF-C9A-D11E-V33A_L50H_I52H mutant in complex with Ni(II) from T. maritima

Summary for 7QC9

• Entry DOI: 10.2210/pdb7qc9/pdb
• Related: 2A0N
• Descriptor: Imidazole glycerol phosphate synthase subunit HisF, NICKEL (II) ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: beta barrel, artificial metalloenzyme, protein design, oxidoreductase, metal binding protein
• Biological source: Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8)
• Total number of polymer chains: 1
• Total formula weight: 28082.65

Authors

Beaumet, M.,Dose, A.,Braeuer, A.,Mahy, J.,Ghattas, W.,Groll, M.,Hess, C. (deposition date: 2021-11-22, release date: 2022-08-10, Last modification date: 2024-01-31)

Primary citation

Beaumet, M.,Dose, A.,Brauer, A.,Mahy, J.P.,Ghattas, W.,Groll, M.,Hess, C.R.
An artificial metalloprotein with metal-adaptive coordination sites and Ni-dependent quercetinase activity.
J.Inorg.Biochem., 235:111914-111914, 2022

PubMed Abstract: Engineering non-native metal active sites into proteins using canonical amino acids offers many advantages but is hampered by significant challenges. The TIM barrel protein, imidazole glycerol phosphate synthase from the hyperthermophilic organism Thermotoga maritima (tHisF), is well-suited for the construction of artificial metalloenzymes by this approach. To this end, we have generated a tHisF variant (tHisF) with a Glu/His/His motif for metal ion coordination. Crystal structures of Zn:tHisF and Ni:tHisF reveal that both metal ions bind to the engineered histidines. However, the two metals bind at distinct sites with different geometries, demonstrating the adaptability of tHisF. Only Zn additionally ligates the Glu residue and adopts a tetrahedral geometry. The pseudo-octahedral Ni site comprises the two His and a native Ser residue. Ni:tHisF catalyzes the oxidative cleavage of the flavanols quercetin and myricetin, providing an unprecedented example of an artificial metalloprotein with quercetinase activity.

PubMed: 35841720
DOI: 10.1016/j.jinorgbio.2022.111914

Experimental method

X-RAY DIFFRACTION (1.8 Å)