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7X7Z

The crystal structure of 2+2/4+2 cyclase PloI4

Summary for 7X7Z
Entry DOI10.2210/pdb7x7z/pdb
DescriptorPloI4 (2 entities in total)
Functional Keywordsploi4, 2+2/4+2 cyclase, lyase
Biological sourceMicromonospora sp.
Total number of polymer chains4
Total formula weight61992.64
Authors
Li, M.,Pan, L.F. (deposition date: 2022-03-10, release date: 2023-02-08, Last modification date: 2023-11-29)
Primary citationWang, H.,Zou, Y.,Li, M.,Tang, Z.,Wang, J.,Tian, Z.,Strassner, N.,Yang, Q.,Zheng, Q.,Guo, Y.,Liu, W.,Pan, L.,Houk, K.N.
A cyclase that catalyses competing 2 + 2 and 4 + 2 cycloadditions.
Nat.Chem., 15:177-184, 2023
Cited by
PubMed Abstract: Cycloaddition reactions are among the most widely used reactions in chemical synthesis. Nature achieves these cyclization reactions with a variety of enzymes, including Diels-Alderases that catalyse concerted 4 + 2 cycloadditions, but biosynthetic enzymes with 2 + 2 cyclase activity have yet to be discovered. Here we report that PloI4, a β-barrel-fold protein homologous to the exo-selective 4 + 2 cyclase that functions in the biosynthesis of pyrroindomycins, catalyses competitive 2 + 2 and 4 + 2 cycloaddition reactions. PloI4 is believed to catalyse an endo-4 + 2 cycloaddition in the biosynthesis of pyrrolosporin A; however, when the substrate precursor of pyrroindomycins was treated with PloI4, an exo-2 + 2 adduct was produced in addition to the exo- and endo-4 + 2 adducts. Biochemical characterizations, computational analyses, (co)crystal structures and mutagenesis outcomes have allowed the catalytic versatility of PloI4 to be rationalized. Mechanistic studies involved the directed engineering of PloI4 to variants that produced the exo-4 + 2, endo-4 + 2 or exo-2 + 2 product preferentially. This work illustrates an enzymatic thermal 2 + 2 cycloaddition and provides evidence of a process through which an enzyme evolves along with its substrate for specialization and activity improvement.
PubMed: 36690833
DOI: 10.1038/s41557-022-01104-x
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.903 Å)
Structure validation

226707

数据于2024-10-30公开中

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