Crystal structure and molecular dynamics studies of L-amino acid oxidase from Bothrops atrox

Feliciano, P.R.; Rustiguel, Joane K.; Soares, Ricardo Oliveira dos Santos; Sampaio, Suely Vilela; Nonato, Maria Cristina

doi:10.1016/j.toxicon.2017.01.017

Cited by 15 publications

(13 citation statements)

References 40 publications

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“…The mature protein of SV-LAAO contains 486 amino acid residues that fold into a multidomain protein comprising of three distinct domains namely: a FAD-binding domain, a substratebinding domain and a helical domain (Figures 2A-D) (Moustafa et al, 2006;Georgieva et al, 2011;Ullah et al, 2012a;Zhang et al, 2004;Feliciano et al, 2017). The overall three-dimensional structure of LAAO is composed of seventeen alpha-helices, twenty-two beta-strands and many loops that fold into three well-defined domains.…”

Section: Overall Structurementioning

confidence: 99%

“…Zinc ions have been found in the crystal structure of LAAOs from Vipera ammodytes ammodytes and B. atrox (Georgieva et al, 2011;Feliciano et al, 2017). Both enzymes were crystallized in the presence of zinc (zinc acetate and zinc sulfate) (Georgieva et al, 2011;Feliciano et al, 2017).…”

Section: Zinc Binding Sitesmentioning

confidence: 99%

“…LAAO is a glycoprotein with molecular mass ranging from 120-150 kDa in native (dimeric) form and 55-66 kDa in the denatured (monomeric form) (Tan and Saifuddin, 1989;Abe et al, 1998). Some reports have also shown their tetrameric existence (Georgieva et al, 2011;Feliciano et al, 2017), however, SV-LAAO is mostly present as a dimer in the solution and it is active in this state (Moustafa et al, 2006;Ullah et al, 2012b). The pI of these enzymes ranges from 4.4 to 8.0 (Tan, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Currently, the crystal structures of six LAAOs have been deposited to the PDB (Zhang et al, 2004;Moustafa et al, 2006;Georgieva et al, 2011;Ullah et al, 2012b;Feliciano et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…They all share the same structural fold which contains three domains: a FAD-binding domain, a substrate-binding domain and a helical domain (Moustafa et al, 2006;Georgieva et al, 2011;Ullah et al, 2012a;Zhang et al, 2004;Feliciano et al, 2017). SV-LAAOs are usually glycosylated and contain about 3-4% carbohydrates in their structure (deKok and Rawitch (1969); Hayes and Wellner, 1969) and in some cases, the carbohydrate contents may be up to 12% of the total molecular mass of the protein (Alves et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Structure–Function Studies and Mechanism of Action of Snake Venom L-Amino Acid Oxidases

Ullah

2020

Front. Pharmacol.

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Snake venom L-amino acid oxidases (SV-LAAOs) are the least studied venom enzymes. These enzymes catalyze the stereospecific oxidation of an L-amino acid to their corresponding a-keto acid with the liberation of hydrogen peroxide (H 2 O 2) and ammonia (NH 3). They display various pathological and physiological activities including induction of apoptosis, edema, platelet aggregation/inhibition, hemorrhagic, and anticoagulant activities. They also show antibacterial, antiviral and leishmanicidal activity and have been used as therapeutic agents in some disease conditions like cancer and anti-HIV drugs. Although the crystal structures of six SV-LAAOs are present in the Protein Data Bank (PDB), there is no single article that describes all of them in particular. To better understand their structural properties and correlate it with their function, the current work describes structure characterization, structure-based mechanism of catalysis, inhibition and substrate specificity of SV-LAAOs. Sequence analysis indicates a high sequence identity (>84%) among SV-LAAOs, comparatively lower sequence identity with Pig kidney D-amino acid oxidase (<50%) and very low sequence identity (<24%) with bacterial LAAOs, Fugal (L-lysine oxidase), and Zea mays Polyamine oxidase (PAAO). The three-dimensional structure of these enzymes are composed of three-domains, a FAD-binding domain, a substrate-binding domain and a helical domain. The sequence and structural analysis indicate that the amino acid residues in the loops vary in length and composition due to which the surface charge distribution also varies that may impart variable substrate specificity to these enzymes. The active site cavity volume and its average depth also vary in these enzymes. The inhibition of these enzymes by synthetic inhibitors will lead to the production of more potent antivenoms against snakebite envenomation.

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Section: Overall Structurementioning

confidence: 99%

Section: Zinc Binding Sitesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Currently, the crystal structures of six LAAOs have been deposited to the PDB (Zhang et al, 2004;Moustafa et al, 2006;Georgieva et al, 2011;Ullah et al, 2012b;Feliciano et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Structure–Function Studies and Mechanism of Action of Snake Venom L-Amino Acid Oxidases

Ullah

2020

Front. Pharmacol.

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Metal coordination by L-amino acid oxidase derived from flounder Platichthys stellatus is structurally essential and regulates antibacterial activity

Kasai

Ito

Nitta

et al. 2020

Appl Microbiol Biotechnol

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Antimicrobial properties of L-amino acid oxidase: biochemical features and biomedical applications

Kasai

Nakano

Ohishi

et al. 2021

Appl Microbiol Biotechnol

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Mucus layer that covers the body surface of various animal functions as a defense barrier against microbes, environmental xenobiotics, and predators. Previous studies have reported that L-amino acid oxidase (LAAO), present in several animal fluids, has potent properties against pathogenic bacteria, viruses, and parasites. LAAO catalyzes the oxidative deamination of specific L-amino acids with the generation of hydrogen peroxide and L-amino acid metabolites. Further, the generated hydrogen peroxide is involved in oxidation (direct effect) while the metabolites activate immune responses (indirect effect). Therefore, LAAO exhibits two different mechanisms of bioactivation. Previously, we described the selective, specific, and local oxidative and potent antibacterial actions of various LAAOs as potential therapeutic strategies. In this review, we focus on their biochemical features, enzymatic regulations, and biomedical applications with a view of describing their probable role as biochemical agents and biomarkers for microbial infections, cancer, and autoimmune-mediated diseases. We consider that LAAOs hold implications in biomedicine owing to their antimicrobial activity wherein they can be used in treatment of infectious diseases and as diagnostic biomarkers in the above-mentioned diseased conditions. Key points •Focus on biochemical features, enzymatic regulation, and biomedical applications of LAAOs. •Mechanisms of antimicrobial activity, inflammatory regulation, and immune responses of LAAOs. •Potential biomedical application as an antimicrobial and anti-infection agent, and disease biomarker.

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Crystal structure and molecular dynamics studies of L-amino acid oxidase from Bothrops atrox

Cited by 15 publications

References 40 publications

Structure–Function Studies and Mechanism of Action of Snake Venom L-Amino Acid Oxidases

Structure–Function Studies and Mechanism of Action of Snake Venom L-Amino Acid Oxidases

Metal coordination by L-amino acid oxidase derived from flounder Platichthys stellatus is structurally essential and regulates antibacterial activity

Antimicrobial properties of L-amino acid oxidase: biochemical features and biomedical applications

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