title: Residue Val237 is critical for the enantioselectivity of Penicillium expansum lipase.
abstract: The shape of the hydrophobic tunnel leading to the active site of Penicillium expansum lipase (PEL) was redesigned by single-point mutations, in order to better understand enzyme enantioselectivity towards naproxen. A variant with a valine-to-glycine substitution at residue 237 exhibited almost no enantioselectivity (E = 1.1) compared with that (E = 104) of wild-type PEL. The function of the residue, Val237, in the hydrophobic tunnel was further analyzed by site-directed mutagenesis. For each of these variants a significant decrease of enantioselectivity (E < 7) was observed compared with that of wild-type enzyme. Further docking result showed that Val237 plays the most important role in stabilizing the correct orientation of (R)-naproxen. Overall, these results indicate that the residue Val237 is the key amino acid residue maintaining the enantioselectivity of the lipase.
authors: College of Life Sciences, Fujian Normal University, Fuzhou, 350108, China, biotlh@gmail.com.
authors: Lianghua
authors: L
authors: Tang
authors: Min
authors: M
authors: Su
authors: Liying
authors: L
authors: Chi
authors: Junling
authors: J
authors: Zhang
authors: Huihui
authors: H
authors: Zhang
authors: Ling
authors: L
authors: Zhu
mesh_terms: D020134:Catalytic Domain; D004252:DNA Mutational Analysis; D008049:Lipase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009288:Naproxen / Q000378:metabolism*; D010407:Penicillium / Q000201:enzymology*; D011487:Protein Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity; D014633:Valine / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D009288:Naproxen; D008049:Lipase; D014633:Valine