8J87

Asfv topoisomerase 2 - apo conformer Ia

Summary for 8J87

• Entry DOI: 10.2210/pdb8j87/pdb
• EMDB information: 36062
• Descriptor: DNA topoisomerase 2 (1 entity in total)
• Functional Keywords: topoisomerase, asfv, isomerase
• Biological source: African swine fever virus
• Total number of polymer chains: 2
• Total formula weight: 272845.16

Authors

Chang, C.-W.,Tsai, M.-D. (deposition date: 2023-05-01, release date: 2024-02-07, Last modification date: 2024-04-17)

Primary citation

Chang, C.M.,Wang, S.C.,Wang, C.H.,Pang, A.H.,Yang, C.H.,Chang, Y.K.,Wu, W.J.,Tsai, M.D.
A unified view on enzyme catalysis by cryo-EM study of a DNA topoisomerase.
Commun Chem, 7:45-45, 2024

PubMed Abstract: The theories for substrate recognition in enzyme catalysis have evolved from lock-key to induced fit, then conformational selection, and conformational selection followed by induced fit. However, the prevalence and consensus of these theories require further examination. Here we use cryogenic electron microscopy and African swine fever virus type 2 topoisomerase (AsfvTop2) to demonstrate substrate binding theories in a joint and ordered manner: catalytic selection by the enzyme, conformational selection by the substrates, then induced fit. The apo-AsfvTop2 pre-exists in six conformers that comply with the two-gate mechanism directing DNA passage and release in the Top2 catalytic cycle. The structures of AsfvTop2-DNA-inhibitor complexes show that substantial induced-fit changes occur locally from the closed apo-conformer that however is too far-fetched for the open apo-conformer. Furthermore, the ATPase domain of AsfvTop2 in the MgAMP-PNP-bound crystal structures coexist in reduced and oxidized forms involving a disulfide bond, which can regulate the AsfvTop2 function.

PubMed: 38418525
DOI: 10.1038/s42004-024-01129-y

Experimental method

ELECTRON MICROSCOPY (3.42 Å)