7ZQ3

Crystal structure of photosynthetic glyceraldehyde-3-phosphate dehydrogenase from Chlamydomonas reinhardtii (CrGAPA) complexed with NADP+

7ZQ3 の概要

• エントリーDOI: 10.2210/pdb7zq3/pdb
• 分子名称: Glyceraldehyde-3-phosphate dehydrogenase A, chloroplastic, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, rossman-fold domain, calvin-benson cycle, pyridin dinucleotide cofactors.
• 由来する生物種: Chlamydomonas reinhardtii
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78206.61

構造登録者

Fermani, S.,Zaffagnini, M.,Lemaire, S.D.,Falini, G.,Fanti, S.,Rossi, J. (登録日: 2022-04-29, 公開日: 2022-07-20, 最終更新日: 2024-01-31)

主引用文献

Mattioli, E.J.,Rossi, J.,Meloni, M.,De Mia, M.,Marchand, C.H.,Tagliani, A.,Fanti, S.,Falini, G.,Trost, P.,Lemaire, S.D.,Fermani, S.,Calvaresi, M.,Zaffagnini, M.
Structural snapshots of nitrosoglutathione binding and reactivity underlying S-nitrosylation of photosynthetic GAPDH.
Redox Biol, 54:102387-102387, 2022

PubMed Abstract: S-nitrosylation is a redox post-translational modification widely recognized to play an important role in cellular signaling as it can modulate protein function and conformation. At the physiological level, nitrosoglutathione (GSNO) is considered the major physiological NO-releasing compound due to its ability to transfer the NO moiety to protein thiols but the structural determinants regulating its redox specificity are not fully elucidated. In this study, we employed photosynthetic glyceraldehyde-3-phosphate dehydrogenase from Chlamydomonas reinhardtii (CrGAPA) to investigate the molecular mechanisms underlying GSNO-dependent thiol oxidation. We first observed that GSNO causes reversible enzyme inhibition by inducing S-nitrosylation. While the cofactor NADP partially protects the enzyme from GSNO-mediated S-nitrosylation, protein inhibition is not observed in the presence of the substrate 1,3-bisphosphoglycerate, indicating that the S-nitrosylation of the catalytic Cys149 is responsible for CrGAPA inactivation. The crystal structures of CrGAPA in complex with NADP and NAD reveal a general structural similarity with other photosynthetic GAPDH. Starting from the 3D structure, we carried out molecular dynamics simulations to identify the protein residues involved in GSNO binding. The reaction mechanism of GSNO with CrGAPA Cys149 was investigated by quantum mechanical/molecular mechanical calculations, which permitted to disclose the relative contribution of protein residues in modulating the activation barrier of the trans-nitrosylation reaction. Based on our findings, we provide functional and structural insights into the response of CrGAPA to GSNO-dependent regulation, possibly expanding the mechanistic features to other protein cysteines susceptible to be oxidatively modified by GSNO.

PubMed: 35793584
DOI: 10.1016/j.redox.2022.102387
主引用文献が同じPDBエントリー

実験手法

X-RAY DIFFRACTION (1.5 Å)