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Structure of MA1831 from Methanosarcina acetivorans in complex with farnesyl thiopyrophosphate and isopentyl S-thiolodiphosphateStructure of MA1831 from Methanosarcina acetivorans in complex with farnesyl thiopyrophosphate and isopentyl S-thiolodiphosphate
Structural highlights
FunctionPublication Abstract from PubMedIsoprenoids represent the largest group of natural products, whose basal skeletons are synthesized by various isoprenyl diphosphate synthases (IDSs). As majority of IDSs catalyze head-to-tail reaction to produce linear form isoprenoids, some catalyze head-to-middle reaction to produce branched form products. In a previous study, an IDS termed MA1831 from Methanosarcina acetivorans was found to be capable of catalyzing both types of reaction. In addition to the canonical linear product of C35 in length, MA1831 also catalyzes head-to-middle condensation of farnesyl diphosphate (FPP) and dimethylallyl diphosphate (DMAPP) to produce geranyllavandulyl diphosphate. In order to investigate the mechanism of action of MA1831, we determined its crystal structures in apo-form and in complex with substrates and analogues. The complex structures that contain isopentenyl S-thiolodiphosphate and DMAPP as homoallylic substrates were also reported, which should represent the reaction modes of MA1831-mediated head-to-tail and head-to-middle reaction, respectively. Based on the structural information, the mechanism of MA1831 catalyze head-to-tail and head-to-middle condensation reaction was proposed. Structural insights to a bi-functional isoprenyl diphosphate synthase that can catalyze head-to-tail and head-to-middle condensation.,Zhang L, Zhang X, Min J, Liu B, Huang JW, Yang Y, Liu W, Dai L, Yang Y, Chen CC, Guo RT Int J Biol Macromol. 2022 Aug 1;214:492-499. doi: 10.1016/j.ijbiomac.2022.06.146., Epub 2022 Jun 25. PMID:35764165[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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