1MO2

Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE), pH 8.5

1MO2 の概要

• エントリーDOI: 10.2210/pdb1mo2/pdb
• 関連するPDBエントリー: 1KEZ 1MN6 1MNA 1MNQ
• 分子名称: Erythronolide synthase, modules 5 and 6 (2 entities in total)
• 機能のキーワード: thioesterase, polyketide synthase, open substrate channel, te, pks, alpha beta hydrolase, 6-deoxyerythronolide, picromycin, pikromycin, erythromycin, transferase
• 由来する生物種: Saccharopolyspora erythraea
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62567.80

構造登録者

Tsai, S.-C.,Lu, H.,Cane, D.E.,Khosla, C.,Stroud, R.M. (登録日: 2002-09-05, 公開日: 2003-02-04, 最終更新日: 2024-02-14)

主引用文献

Tsai, S.-C.,Lu, H.,Cane, D.E.,Khosla, C.,Stroud, R.M.
Insights into channel architecture and substrate specificity from crystal structures of two macrocycle-forming thioesterases of modular polyketide synthases
Biochemistry, 41:12598-12606, 2002

PubMed Abstract: Modular polyketide synthases (PKSs) synthesize the polyketide cores of pharmacologically important natural products such as erythromycin and picromycin. Understanding PKSs at high resolution could present new opportunities for chemoenzymatic synthesis of complex molecules. The crystal structures of macrocycle-forming thioesterase (TE) domains from the picromycin synthase (PICS) and 6-deoxyerythronolide B synthase (DEBS) were determined to 1.8-3.0 A with an R(crys) of 19.2-24.4%, including three structures of PICS TE (crystallized at pH 7.6, 8.0, and 8.4) and a second crystal form of DEBS TE. As predicted by the previous work on DEBS TE [Tsai, S. C., et al. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 14808-14813], PICS TE contains an open substrate channel and a hydrophobic dimer interface. Notwithstanding their similarity, the dimer interfaces and substrate channels of DEBS TE and PICS TE reveal key differences. The structural basis for the divergent substrate specificities of DEBS TE and PICS TE is analyzed. The size of the substrate channel increases with increasing pH, presumably due to electrostatic repulsion in the channel at elevated pH. Together, these structures support previous predictions that macrocycle-forming thioesterases from PKSs share the same protein fold, an open substrate channel, a similar catalytic mechanism, and a hydrophobic dimer interface. They also provide a basis for the design of enzymes capable of catalyzing regioselective macrocyclization of natural or synthetic substrates. A series of high-resolution snapshots of a protein channel at different pHs is presented alongside analysis of channel residues, which could help in the redesign of the protein channel architecture.

PubMed: 12379102
DOI: 10.1021/bi0260177

実験手法

X-RAY DIFFRACTION (3 Å)