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Crystal structure of a membrane-bound l-amino acid deaminase from Proteus vulgaris.

Ju Y, Tong S, Gao Y, Zhao W, Liu Q, Gu Q, Xu J, Niu L, Teng M, Zhou H
J Struct Biol 195 306-315 (2016)
Cited: 14 times
EuropePMC logo PMID: 27422658

Abstract

l-amino acid oxidases/deaminases (LAAOs/LAADs) are a class of oxidoreductases catalyzing the oxidative deamination of l-amino acids to α-keto acids. They are widely distributed in eukaryotic and prokaryotic organisms, and exhibit diverse substrate specificity, post-translational modifications and cellular localization. While LAAOs isolated from snake venom have been extensively characterized, the structures and functions of LAAOs from other species are largely unknown. Here, we reported crystal structure of a bacterial membrane-bound LAAD from Proteus vulgaris (pvLAAD) in complex with flavin adenine dinucleotide (FAD). We found that the overall fold of pvLAAD does not resemble typical LAAOs. Instead it, is similar to d-amino acid oxidases (DAAOs) with an additional hydrophobic insertion module on protein surface. Structural analysis and liposome-binding assays suggested that the hydrophobic module serves as an extra membrane-binding site for LAADs. Bacteria from genera Proteus and Providencia were found to encode two classes of membrane-bound LAADs. Based on our structure, the key roles of residues Q278 and L317 in substrate selectivity were proposed and biochemically analyzed. While LAADs on the membrane were proposed to transfer electrons to respiratory chain for FAD re-oxidization, we observed that the purified pvLAAD could generate a significant amount of hydrogen peroxide in vitro, suggesting it could use dioxygen to directly re-oxidize FADH2 as what typical LAAOs usually do. These findings provide a novel insights for a better understanding this class of enzymes and will help developing biocatalysts for industrial applications.

Articles - 5hxw mentioned but not cited (4)

  1. Membrane binding of the insertion sequence of Proteus vulgaris L-amino acid deaminase stabilizes protein structure and increases catalytic activity. Ju Y, Liu Z, Zhang Z, Duan L, Liu Q, Gu Q, Zhang C, Xu J, Zhou H. Sci Rep 7 13719 (2017)
  2. Synthesis, spectroscopic findings, SEM/EDX, DFT, and single-crystal structure of Hg/Pb/Cu-SCN complexes: In silico ADME/T profiling and promising antibacterial activities. Majumdar D, Philip JE, Dubey A, Tufail A, Roy S. Heliyon 9 e16103 (2023)
  3. Cytotoxic and Infection-Controlled Investigations of Novel Dihydropyridine Hybrids: An Efficient Synthesis and Molecular-Docking Studies. Guda MR, Zyryanov GV, Dubey A, Munagapati VS, Wen JC. Pharmaceuticals (Basel) 16 1159 (2023)
  4. Semi-rational engineering membrane binding domain of L-amino acid deaminase from Proteus vulgaris for enhanced α-ketoisocaproate. Song Y, Wang R, Zhang Z, Liu X, Qi L, Shentu X, Yu X. Front Microbiol 13 1025845 (2022)


Reviews citing this publication (3)

  1. Breaking the mirror: l-Amino acid deaminase, a novel stereoselective biocatalyst. Molla G, Melis R, Pollegioni L. Biotechnol Adv 35 657-668 (2017)
  2. Engineering of L-amino acid deaminases for the production of α-keto acids from L-amino acids. Nshimiyimana P, Liu L, Du G. Bioengineered 10 43-51 (2019)
  3. Recent advances in biocatalytic derivatization of L-tyrosine. Tan X, Song W, Chen X, Liu L, Wu J. Appl Microbiol Biotechnol 104 9907-9920 (2020)

Articles citing this publication (7)

  1. X-shaped structure of bacterial heterotetrameric tRNA synthetase suggests cryptic prokaryote functions and a rationale for synthetase classifications. Ju Y, Han L, Chen B, Luo Z, Gu Q, Xu J, Yang XL, Schimmel P, Zhou H. Nucleic Acids Res 49 10106-10119 (2021)
  2. [Cu(dipicolinoylamide)(NO3)(H2O)] as anti-COVID-19 and antibacterial drug candidate: Design, synthesis, crystal structure, DFT and molecular docking. Abdel-Rahman LH, Basha MT, Al-Farhan BS, Shehata MR, Mohamed SK, Ramli Y. J Mol Struct 1247 131348 (2022)
  3. Tuning the transcription and translation of L-amino acid deaminase in Escherichia coli improves α-ketoisocaproate production from L-leucine. Song Y, Li J, Shin HD, Liu L, Du G, Chen J. PLoS One 12 e0179229 (2017)
  4. Ancestral L-amino acid oxidases for deracemization and stereoinversion of amino acids. Nakano S, Kozuka K, Minamino Y, Karasuda H, Hasebe F, Ito S. Commun Chem 3 181 (2020)
  5. Efficient production of α-keto acids by immobilized E. coli-pETduet-1-PmiLAAO in a jacketed packed-bed reactor. Wu L, Guo X, Wu G, Liu P, Liu Z. R Soc Open Sci 6 182035 (2019)
  6. Production of Salvianic Acid A from l-DOPA via Biocatalytic Cascade Reactions. Hu KS, Chen CL, Ding HR, Wang TY, Zhu Q, Zhou YC, Chen JM, Mei JQ, Hu S, Huang J, Zhao WR, Mei LH. Molecules 27 6088 (2022)
  7. Synthesis, spectroscopic investigation, molecular docking, ADME/T toxicity predictions, and DFT study of two trendy ortho vanillin-based scaffolds. Majumdar D, Dubey A, Tufail A, Sutradhar D, Roy S. Heliyon 9 e16057 (2023)


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