7dmo
From Proteopedia
Crystal structures of two pericyclases catalyzing [4+2] cycloadditions
Structural highlights
FunctionPHM7_PYRSX Diels-Alderase; part of the gene cluster that mediates the biosynthesis of the trans-fused decalin-containing tetramic acid phomasetin, the stereochemical opposite of the HIV-1 integrase inhibitor equisetin (PubMed:29972614). The PKS module of phm1 together with the enoylreductase phm4 catalyze the formation of the polyketide unit which is then conjugated to L-serine by the condensation domain of the phm1 NRPS module (PubMed:29972614). Activity of the Dieckmann cyclase domain (RED) of phm1 results in release of the Dieckmann product intermediate (PubMed:29972614). The Diels-Alderase phm7 then uses the Dieckmann product of phm1 as substrate and catalyzes the Diels-Alder cycloaddition to form the decalin ring of N-desmethylphomasetin (PubMed:29972614, PubMed:34121297). N-desmethylphomasetin is further methylated to phomasetin by the methyltransferase phm5 (PubMed:29972614).[1] [2] Publication Abstract from PubMedFsa2 and Phm7 are a unique pair of pericyclases catalyzing [4 + 2] cycloaddition reactions with reverse stereoselectivities in the biosynthesis of equisetin and phomasetin, both of which are potent HIV-1 integrase inhibitors. We here solve the crystal structures of Fsa2 and Phm7, both of which possess unusual "two-beta barrel" folds. Different residues are evident between the active sites of Fsa2 and Phm7, and modeling experiments provide key structural information determining the reverse stereoselectivities. These results provide a better understanding of how natural pericyclases control the catalytic stereoselectivities and benefit the protein engineering in future. Crystal Structures of Fsa2 and Phm7 Catalyzing [4 + 2] Cycloaddition Reactions with Reverse Stereoselectivities in Equisetin and Phomasetin Biosynthesis.,Chi C, Wang Z, Liu T, Zhang Z, Zhou H, Li A, Jin H, Jia H, Yin F, Yang D, Ma M ACS Omega. 2021 May 6;6(19):12913-12922. doi: 10.1021/acsomega.1c01593., eCollection 2021 May 18. PMID:34056443[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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