Structural highlights
FunctionHIS6_THEMA IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The HisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the HisH subunit.[HAMAP-Rule:MF_01013] Publication Abstract from PubMedEngineering 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(EHH)) with a Glu/His/His motif for metal ion coordination. Crystal structures of Zn(II):tHisF(EHH) and Ni(II):tHisF(EHH) 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(II) additionally ligates the Glu residue and adopts a tetrahedral geometry. The pseudo-octahedral Ni(II) site comprises the two His and a native Ser residue. Ni(II):tHisF(EHH) catalyzes the oxidative cleavage of the flavanols quercetin and myricetin, providing an unprecedented example of an artificial metalloprotein with quercetinase activity. An artificial metalloprotein with metal-adaptive coordination sites and Ni-dependent quercetinase activity.,Beaumet M, Dose A, Brauer A, Mahy JP, Ghattas W, Groll M, Hess CR J Inorg Biochem. 2022 Jul 6;235:111914. doi: 10.1016/j.jinorgbio.2022.111914. PMID:35841720[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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