1EUH

APO FORM OF A NADP DEPENDENT ALDEHYDE DEHYDROGENASE FROM STREPTOCOCCUS MUTANS

1EUH の概要

• エントリーDOI: 10.2210/pdb1euh/pdb
• 分子名称: NADP DEPENDENT NON PHOSPHORYLATING GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE, SULFATE ION (3 entities in total)
• 機能のキーワード: dehydrogenase, oxidoreductase
• 由来する生物種: Streptococcus mutans
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 206066.38

構造登録者

Cobessi, D.,Tete-Favier, F.,Marchal, S.,Branlant, G.,Aubry, A. (登録日: 1998-11-05, 公開日: 1999-07-22, 最終更新日: 2024-05-22)

主引用文献

Cobessi, D.,Tete-Favier, F.,Marchal, S.,Azza, S.,Branlant, G.,Aubry, A.
Apo and holo crystal structures of an NADP-dependent aldehyde dehydrogenase from Streptococcus mutans.
J.Mol.Biol., 290:161-173, 1999

PubMed Abstract: The aldehyde dehydrogenases (ALDHs) are a superfamily of multimeric enzymes which catalyse the oxidation of a broad range of aldehydes into their corresponding carboxylic acids with the reduction of their cofactor, NAD or NADP, into NADH or NADPH. At present, the only known structures concern NAD-dependent ALDHs. Three structures are available in the Protein Data Bank: two are tetrameric and the other is a dimer. We solved by molecular replacement the first structure of an NADP-dependent ALDH isolated from Streptococcus mutans, in its apo form and holo form in complex with NADP, at 1.8 and 2.6 A resolution, respectively. Although the protein sequence shares only approximately 30 % identity with the other solved tetrameric ALDHs, the structures are very similar. However, a large local conformational change in the region surrounding the 2' phosphate group of the adenosine moiety is observed when the enzyme binds NADP, in contrast to the NAD-dependent ALDHs. Structure and sequence analyses reveal several properties. A small number of residues seem to determine the oligomeric state. Likewise, the nature (charge and volume) of the residue at position 180 (Thr in ALDH from S. mutans) determines the cofactor specificity in comparison with the structures of NAD-dependent ALDHs. The presence of a hydrogen bond network around the cofactor not only allows it to bind to the enzyme but also directs the side-chains in a correct orientation for the catalytic reaction to take place. Moreover, a specific part of this network appears to be important in substrate binding. Since the enzyme oxidises the same substrate, glyceraldehyde-3-phosphate (G3P), as NAD-dependent phosphorylating glyceraldehyde-3-phosphate dehydrogenases (GAPDH), the active site of GAPDH was compared with that of the S. mutans ALDH. It was found that Arg103, Arg283 and Asp440 might be key residues for substrate binding.

PubMed: 10388564
DOI: 10.1006/jmbi.1999.2853

実験手法

X-RAY DIFFRACTION (1.82 Å)