3QGO

Structure of Thermolysin in complex with L-Phenylalanine methylester

3QGO の概要

• エントリーDOI: 10.2210/pdb3qgo/pdb
• 関連するPDBエントリー: 2TLX 4TMN 5TMN 6TMN 7TLN 8TLN
• 分子名称: Thermolysin, CALCIUM ION, ZINC ION, ... (8 entities in total)
• 機能のキーワード: hydrolase, metalloproteinase, l-phenylalanine methyl ester
• 由来する生物種: Bacillus thermoproteolyticus
• 細胞内の位置: Secreted: P00800
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35903.68

構造登録者

Birrane, G.,Bhyravbhatla, B.,Navia, M. (登録日: 2011-01-24, 公開日: 2012-01-04, 最終更新日: 2023-12-06)

主引用文献

Birrane, G.,Bhyravbhatla, B.,Navia, M.A.
Synthesis of Aspartame by Thermolysin: An X-ray Structural Study.
ACS MED.CHEM.LETT., 5:706-710, 2014

PubMed Abstract: Protease mediated peptide synthesis (PMPS) was first described in the 1930s but remains underexploited today. In most PMPS, the reaction equilibrium is shifted toward synthesis by the aqueous insolubility of product generated. Substrates and proteases are selected by trial and error, yields are modest, and reaction times are slow. Once implemented, however, PMPS reactions can be simple, environmentally benign, and readily scalable to a commercial level. We examined the PMPS of a precursor of the artificial sweetener aspartame, a multiton peptide synthesis catalyzed by the enzyme thermolysin. X-ray structures of thermolysin in complex with aspartame substrates separately, and after PMPS in a crystal, rationalize the reaction's substrate preferences and reveal an unexpected form of substrate inhibition that explains its sluggishness. Structure guided optimization of this and other PMPS reactions could expand the economic viability of commercial peptides beyond current high-potency, low-volume therapeutics, with substantial green chemistry advantages.

PubMed: 24944748
DOI: 10.1021/ml500101z

実験手法

X-RAY DIFFRACTION (1.45 Å)