7D4S

apo-form cyclic trinucleotide synthase CdnD

7D4S の概要

• エントリーDOI: 10.2210/pdb7d4s/pdb
• 関連するPDBエントリー: 7D48 7D4J 7D4O 7D4U
• 分子名称: Cyclic AMP-AMP-GMP synthase, DIPHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: substrate analogue cyclic trinucleotide synthesis nucleotidyl transferase, transferase
• 由来する生物種: Enterobacter cloacae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45486.28

構造登録者

Yang, C.-S.,Hou, M.-H.,Tsai, C.-L.,Wang, Y.-C.,Ko, T.-P.,Chen, Y. (登録日: 2020-09-24, 公開日: 2021-03-17, 最終更新日: 2023-11-29)

主引用文献

Ko, T.P.,Wang, Y.C.,Tsai, C.L.,Yang, C.S.,Hou, M.H.,Chen, Y.
Crystal structure and functional implication of a bacterial cyclic AMP-AMP-GMP synthetase.
Nucleic Acids Res., 49:4725-4737, 2021

PubMed Abstract: Mammalian cyclic GMP-AMP synthase (cGAS) and its homologue dinucleotide cyclase in Vibrio cholerae (VcDncV) produce cyclic dinucleotides (CDNs) that participate in the defense against viral infection. Recently, scores of new cGAS/DncV-like nucleotidyltransferases (CD-NTases) were discovered, which produce various CDNs and cyclic trinucleotides (CTNs) as second messengers. Here, we present the crystal structures of EcCdnD, a CD-NTase from Enterobacter cloacae that produces cyclic AMP-AMP-GMP, in its apo-form and in complex with ATP, ADP and AMPcPP, an ATP analogue. Despite the similar overall architecture, the protein shows significant structural variations from other CD-NTases. Adjacent to the donor substrate, another nucleotide is bound to the acceptor binding site by a non-productive mode. Isothermal titration calorimetry results also suggest the presence of two ATP binding sites. GTP alone does not bind to EcCdnD, which however binds to pppApG, a possible intermediate. The enzyme is active on ATP or a mixture of ATP and GTP, and the best metal cofactor is Mg2+. The conserved residues Asp69 and Asp71 are essential for catalysis, as indicated by the loss of activity in the mutants. Based on structural analysis and comparison with VcDncV and RNA polymerase, a tentative catalytic pathway for the CTN-producing EcCdnD is proposed.

PubMed: 33836064
DOI: 10.1093/nar/gkab165

実験手法

X-RAY DIFFRACTION (1.93 Å)