7PKC

Streptococcus pyogenes Apo-GapN C284S variant

これはPDB形式変換不可エントリーです。

7PKC の概要

• エントリーDOI: 10.2210/pdb7pkc/pdb
• 分子名称: Putative NADP-dependent glyceraldehyde-3-phosphate dehydrogenase, SULFATE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: apo-enzyme, oxidoreductase
• 由来する生物種: Streptococcus pyogenes M49 591
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 852915.31

構造登録者

Schindelin, H.,Albert, L. (登録日: 2021-08-25, 公開日: 2022-03-16, 最終更新日: 2024-05-01)

主引用文献

Eisenberg, P.,Albert, L.,Teuffel, J.,Zitzow, E.,Michaelis, C.,Jarick, J.,Sehlke, C.,Grosse, L.,Bader, N.,Nunes-Alves, A.,Kreikemeyer, B.,Schindelin, H.,Wade, R.C.,Fiedler, T.
The Non-phosphorylating Glyceraldehyde-3-Phosphate Dehydrogenase GapN Is a Potential New Drug Target in Streptococcus pyogenes.
Front Microbiol, 13:802427-802427, 2022

PubMed Abstract: The strict human pathogen causes infections of varying severity, ranging from self-limiting suppurative infections to life-threatening diseases like necrotizing fasciitis or streptococcal toxic shock syndrome. Here, we show that the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase GapN is an essential enzyme for . GapN converts glyceraldehyde 3-phosphate into 3-phosphoglycerate coupled to the reduction of NADP to NADPH. The knock-down of by antisense peptide nucleic acids (asPNA) significantly reduces viable bacterial counts of laboratory and macrolide-resistant clinical strains . As lacks the oxidative part of the pentose phosphate pathway, GapN appears to be the major NADPH source for the bacterium. Accordingly, other streptococci that carry a complete pentose phosphate pathway are not prone to asPNA-based knock-down. Determination of the crystal structure of the GapN apo-enzyme revealed an unusual cis-peptide in proximity to the catalytic binding site. Furthermore, using a structural modeling approach, we correctly predicted competitive inhibition of GapN by erythrose 4-phosphate, indicating that our structural model can be used for screening of specific GapN inhibitors. In conclusion, the data provided here reveal that GapN is a potential target for antimicrobial substances that selectively kill and other streptococci that lack the oxidative part of the pentose phosphate pathway.

PubMed: 35242116
DOI: 10.3389/fmicb.2022.802427

実験手法

X-RAY DIFFRACTION (1.5 Å)