Enzymatic characterization and crystal structure of biosynthetic alanine racemase from Pseudomonas aeruginosa PAO1

Journal Article · Sat Sep 15 00:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.06.155· OSTI ID:23103644

Dong, Hui ^[1]; Han, Qingqing ^[2]; Guo, Yu ^[3]; Ju, Jiansong ^[2]; Wang, Shanshan ^[3]; Yuan, Chao ^[3]; Long, Wei; He, Xin ^[1]; Xu, Shujing ^[2]; Li, Sheng ^[3]

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1. Key Laboratory of Tianjin Radiation and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192 (China)
2. College of Life Science, Hebei Normal University, Shijiazhuang, 050024 (China)
3. Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210 (China)

Highlights: • The crystal structure of PaAlr was solved. • Sequences and structures were compared among species with two alanine racemases. • d-Lysine was observed in active site, but not covanlently linked, which is somehow similar but different from PaDadX. • Optimal reaction conditions were characterized. Alanine racemase is a pyridoxal-5′-phosphate (PLP)-dependent enzyme that reversibly catalyzes the conversion of l-alanine to d-alanine. d-alanine is an essential constituent in many prokaryotic cell structures. Inhibition of alanine racemase is lethal to prokaryotes, creating an attractive target for designing antibacterial drugs. Here we report the crystal structure of biosynthetic alanine racemase (Alr) from a pathogenic bacteria Pseudomonas aeruginosa PAO1. Structural studies showed that P. aeruginosa Alr (PaAlr) adopts a conserved homodimer structure. A guest substrate d-lysine was observed in the active site and refined to dual-conformation. Two buffer ions, malonate and acetate, were bound in the proximity to d-lysine. Biochemical characterization revealed the optimal reaction conditions for PaAlr.

• OSTI ID: 23103644
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 503, Issue 4; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALANINE-L
ANTIBIOTICS
ENZYMES
LYSINE
PSEUDOMONAS
PYRIDOXAL