1X2B

The crystal structure of prolyl aminopeptidase complexed with Sar-TBODA

1X2B の概要

• エントリーDOI: 10.2210/pdb1x2b/pdb
• 関連するPDBエントリー: 1QTR 1WM1 1X2E
• 分子名称: Proline iminopeptidase, 1-(5-TERT-BUTYL-1,3,4-OXADIAZOL-2-YL)-2-(METHYLAMINO)ETHANONE (3 entities in total)
• 機能のキーワード: prolyl aminopeptidase, binary complex, prolyl iminopeptidase, alpha/beta-hydrolase, hydrolase
• 由来する生物種: Serratia marcescens
• 細胞内の位置: Cytoplasm: O32449
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36327.83

構造登録者

Nakajima, Y.,Ito, K.,Sakata, M.,Xu, Y.,Matsubara, F.,Hatakeyama, S.,Yoshimoto, T. (登録日: 2005-04-22, 公開日: 2006-05-09, 最終更新日: 2023-10-25)

主引用文献

Nakajima, Y.,Ito, K.,Sakata, M.,Xu, Y.,Nakashima, K.,Matsubara, F.,Hatakeyama, S.,Yoshimoto, T.
Unusual extra space at the active site and high activity for acetylated hydroxyproline of prolyl aminopeptidase from Serratia marcescens
J.Bacteriol., 188:1599-1606, 2006

PubMed Abstract: The prolyl aminopeptidase complexes of Ala-TBODA [2-alanyl-5-tert-butyl-(1, 3, 4)-oxadiazole] and Sar-TBODA [2-sarcosyl-5-tert-butyl-(1, 3, 4)-oxadiazole] were analyzed by X-ray crystallography at 2.4 angstroms resolution. Frames of alanine and sarcosine residues were well superimposed on each other in the pyrrolidine ring of proline residue, suggesting that Ala and Sar are recognized as parts of this ring of proline residue by the presence of a hydrophobic proline pocket at the active site. Interestingly, there was an unusual extra space at the bottom of the hydrophobic pocket where proline residue is fixed in the prolyl aminopeptidase. Moreover, 4-acetyloxyproline-betaNA (4-acetyloxyproline beta-naphthylamide) was a better substrate than Pro-betaNA. Computer docking simulation well supports the idea that the 4-acetyloxyl group of the substrate fitted into that space. Alanine scanning mutagenesis of Phe139, Tyr149, Tyr150, Phe236, and Cys271, consisting of the hydrophobic pocket, revealed that all of these five residues are involved significantly in the formation of the hydrophobic proline pocket for the substrate. Tyr149 and Cys271 may be important for the extra space and may orient the acetyl derivative of hydroxyproline to a preferable position for hydrolysis. These findings imply that the efficient degradation of collagen fragment may be achieved through an acetylation process by the bacteria.

PubMed: 16452443
DOI: 10.1128/JB.188.4.1599-1606.2006

実験手法

X-RAY DIFFRACTION (2.4 Å)