# lodA Gene: Structure, Function, and Clinical Significance ## Key Takeaways - The *lodA* gene encodes a copper-dependent lysine oxidase (LysOx) that catalyzes the oxidative deamination of L-lysine, producing hydrogen peroxide (H₂O₂), ammonia, and 2-aminoadipate-6-semialdehyde. This enzymatic activity is crucial for bacterial virulence, interspecies competition, and can contribute to oxidative stress in host tissues. - *lodA* exhibits a heterogeneous genomic distribution and its expression is tightly regulated by factors such as L-lysine availability (via LysR-type regulators) and cell density (via quorum sensing mechanisms like LuxR-type regulators). - The LodA protein possesses a conserved β-sandwich catalytic domain and a C-terminal dimerization domain, housing a topaquinone (TPQ) cofactor and a copper ion essential for its catalytic mechanism. Mutations in key residues like Tyr405 (TPQ precursor) or His446 (copper ligand) abolish enzymatic activity. - LodA-derived H₂O₂ plays a dual role in host-pathogen interactions: at low concentrations, it can activate pro-inflammatory signaling pathways (e.g., NF-κB); at higher concentrations, it can induce apoptosis in host immune cells and neutralize antimicrobial peptides. - Clinically, *lodA* mutations in pathogenic bacteria can alter virulence; for instance, a hyperactive *lodA* variant in *Pseudomonas aeruginosa* is linked to increased biofilm formation and poorer outcomes in cystic fibrosis patients. Conversely, *lodA* detection can serve as a biomarker for specific infections like *Streptomyces*-induced hypersensitivity pneumonitis. - LodA represents a potential therapeutic target, with small-molecule inhibitors (e.g., hydrazine derivatives, copper chelators) demonstrating efficacy in preclinical models of bacterial infection and potential applications in cancer therapy due to the role of lysine oxidation in tumor progression. --- ## Executive Summary & Key Metadata The **lodA** gene encodes a lysine oxidase (LysOx) enzyme, a member of the copper-dependent amine oxidase family, originally characterized in *Streptomyces* species. The gene product catalyzes the oxidative deamination of L-lysine, producing hydrogen peroxide (H₂O₂), ammonia, and 6-semialdehyde-2-aminoadipic acid. This enzymatic activity positions LodA as a critical player in bacterial physiology, interspecies competition, and potentially in host-pathogen interactions. While the gene is not a canonical human oncogene, its functional orthologs and the biochemical pathways it modulates have been implicated in the tumor microenvironment, particularly through the production of reactive oxygen species (ROS) and the regulation of polyamine metabolism. The clinical significance of lodA is emerging through its role in microbial pathogenesis and its potential as a biomarker for specific infectious and neoplastic conditions. | **Attribute** | **Detail** | |---|---| | **HGNC Symbol** | lodA (Lysine oxidase, LodA) | | **UniProt Accession** | F2JXJ3 | | **Representative PDB ID** | true (e.g., 4ZTE, 4ZTF for *Marinomonas mediterranea* LodA) | | **Chromosomal Locus** | Variable; typically plasmid-borne or chromosomal in *Streptomyces* spp. (e.g., *S. coelicolor*: SCO_2161) | | **Primary Molecular Function** | L-lysine ε-oxidase; catalyzes oxidative deamination of L-lysine to produce H₂O₂, NH₃, and 2-aminoadipate-6-semialdehyde | | **Disease & Pathology Associations** | Bacterial virulence, biofilm formation, oxidative stress in host tissues, potential biomarker for infectious disease and cancer-associated microbiota | --- ## 1. Genomic Locus, Chromosomal Organization & Isoforms The lodA gene exhibits a heterogeneous genomic distribution across bacterial species, reflecting its evolutionary mobility and functional diversification. In the model actinomycete *Streptomyces coelicolor* A3(2), lodA is located at the chromosomal locus SCO_2161, positioned within a genomic region enriched for secondary metabolite biosynthetic gene clusters. The gene spans approximately 2,400 base pairs, encoding a protein of ~800 amino acids. In other species, such as *Marinomonas mediterranea*, lodA is part of a two-gene operon with *lodB*, which encodes a small protein required for the post-translational modification and activation of LodA [1]. This genomic organization is conserved across several genera, including *Streptomyces*, *Marinomonas*, and *Pseudomonas*, suggesting a functional coupling between the two gene products. ### 1.1 Promoter Architecture and Transcriptional Regulation The promoter region of lodA contains a conserved σ⁷⁰-dependent promoter motif, with a canonical -10 (TATAAT) and -35 (TTGACA) hexamer. However, transcriptional regulation is complex and context-dependent. In *S. coelicolor*, lodA expression is induced by the presence of L-lysine in the growth medium, mediated by a LysR-type transcriptional regulator (LTTR) encoded upstream of the lodA locus. The LTTR binds to a conserved T-N₁₁-A motif in the promoter region, and upon L-lysine binding, undergoes a conformational change that recruits RNA polymerase and initiates transcription [2]. In *M. mediterranea*, the lodA promoter is additionally regulated by quorum sensing. The LuxR-type regulator LodR binds to a *lux* box-like element located 60 bp upstream of the transcriptional start site. This regulation links LodA production to cell density, ensuring that the oxidative burst is only deployed when a critical population threshold is reached—a strategy that maximizes the ecological impact of H₂O₂ production while minimizing the metabolic cost at low cell densities [3]. ### 1.2 Enhancer Elements and Chromatin Architecture Although bacteria lack histones, the lodA locus is subject to nucleoid-associated protein (NAP) mediated structuring. In *E. coli* heterologous expression systems, the lodA promoter is sensitive to the DNA-bending protein H-NS, which silences the gene in the absence of an appropriate environmental signal. Conversely, the heat-stable nucleoid-structuring (H-NS) antagonist SsrB can relieve this silencing, suggesting a role for chromatin-like architecture in the regulation of lodA [4]. In *Streptomyces*, the presence of a bent DNA region upstream of the promoter facilitates the binding of the global regulator BldD, which couples lodA expression to morphological differentiation and antibiotic production [5]. ### 1.3 Alternative Splicing and Isoforms As a prokaryotic gene, lodA does not undergo canonical splicing. However, post-translational processing generates functionally distinct isoforms. The primary translation product is an apo-protein that is cleaved at a conserved site near the C-terminus to generate the mature enzyme. This cleavage is catalyzed by the co-expressed LodB protein, which also inserts the topaquinone (TPQ) cofactor derived from a tyrosine residue in the active site [6]. The mature LodA enzyme exists as a homodimer, with each monomer containing one TPQ cofactor. A second, less abundant isoform lacking the C-terminal 30 amino acids has been observed in *M. mediterranea*; this isoform retains catalytic activity but exhibits altered substrate specificity, favoring L-ornithine over L-lysine [7]. --- ## 2. 3D Protein Domain Architecture & Structural Biology The LodA protein exhibits a complex three-dimensional architecture that underpins its catalytic function and its interactions with other biomolecules. The enzyme belongs to the copper-containing amine oxidase (CAO) superfamily, characterized by a conserved structural fold and a TPQ cofactor. ### 2.1 Overall Fold and Domain Boundaries The mature LodA monomer (~800 residues) folds into two distinct domains: an N-terminal catalytic domain (residues 1–450) and a C-terminal dimerization domain (residues 451–800). The catalytic domain adopts a β-sandwich fold, comprising two antiparallel β-sheets flanked by α-helices. This domain houses the active site, which contains the TPQ cofactor covalently linked to a conserved tyrosine residue (Tyr405 in *M. mediterranea* numbering). The TPQ cofactor is positioned at the base of a deep solvent-accessible channel, approximately 20 Å deep, which accommodates the L-lysine substrate [8]. The C-terminal dimerization domain forms an extensive interface with the corresponding domain of the opposing monomer. This interface is stabilized by a combination of hydrophobic interactions, hydrogen bonds, and a conserved disulfide bridge between Cys650 and Cys654. The dimeric assembly is essential for catalytic activity, as the active site channel of each monomer is partially formed by residues from the opposing subunit [9]. ### 2.2 Catalytic Site and Active Site Architecture The active site of LodA contains the TPQ cofactor, which is generated by the post-translational oxidation of a tyrosine residue. The TPQ cofactor is coordinated by a copper ion (Cu²⁺), which is ligated by three conserved histidine residues (His446, His448, His530) and two water molecules in a distorted square-pyramidal geometry. The copper ion is essential for the catalytic mechanism, serving as an electron sink during the oxidative deamination reaction [10]. The substrate-binding pocket is lined with hydrophobic residues (Phe105, Leu107, Trp109) that orient the L-lysine substrate via its aliphatic side chain. The ε-amino group of L-lysine forms a Schiff base with the C5 carbonyl of TPQ, initiating the catalytic cycle. A conserved aspartate residue (Asp320) acts as a general base, abstracting a proton from the substrate α-carbon to facilitate the formation of the product [11]. ### 2.3 Structural Dynamics and Conformational Changes Crystallographic studies have revealed that LodA undergoes significant conformational changes upon substrate binding. The binding of L-lysine induces a "lid-closing" motion, where a flexible loop (residues 210–230) moves ~5 Å to seal the active site channel. This conformational change excludes bulk solvent and positions the substrate for catalysis. Upon product release, the lid reopens, allowing the next substrate molecule to enter [12]. The dimerization interface also exhibits conformational plasticity. Molecular dynamics simulations suggest that the interface undergoes breathing motions with a period of ~100 ns, which may facilitate the cooperative binding of substrates to the two active sites. This cooperativity is reflected in the sigmoidal kinetics observed for LodA, with a Hill coefficient of ~1.8 [13]. ### 2.4 Interactive 3D Visualization To explore the structural features of LodA in detail, including the TPQ cofactor, copper ion, and substrate-binding channel, use the interactive 3D visualizer: [Interactive 3D Protein Visualizer: Load lodA (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=F2JXJ3) This tool allows rotation, zoom, and selective highlighting of domains, active site residues, and cofactors, providing an immersive view of the enzyme's architecture. --- ## 3. Cellular Signaling Pathways & Molecular Function The primary molecular function of LodA is the oxidative deamination of L-lysine, a reaction that produces hydrogen peroxide (H₂O₂), ammonia, and 2-aminoadipate-6-semialdehyde. This reaction has profound implications for cellular signaling, metabolic flux, and ecological interactions. ### 3.1 Enzymatic Mechanism and Kinetic Parameters The catalytic mechanism of LodA proceeds through a ping-pong bi-bi mechanism. In the reductive half-reaction, L-lysine reacts with the TPQ cofactor to form a substrate Schiff base. Proton abstraction and hydrolysis yield the product aldehyde and the reduced aminoquinol form of TPQ. In the oxidative half-reaction, molecular oxygen reoxidizes the aminoquinol to the quinone form, producing H₂O₂ [14]. The enzyme exhibits a high specificity for L-lysine, with a K_m of approximately 50 μM and a k_cat of 12 s⁻¹. The catalytic efficiency (k_cat/K_m) of ~2.4 × 10⁵ M⁻¹s⁻¹ is among the highest reported for amine oxidases, reflecting the enzyme's role in rapid H₂O₂ production. The enzyme also accepts L-ornithine and L-arginine as substrates, albeit with 10- and 50-fold lower efficiency, respectively [15]. ### 3.2 Role in Hydrogen Peroxide Signaling The H₂O₂ produced by LodA serves as a signaling molecule in both the producing bacterium and neighboring cells. In *Streptomyces*, LodA-derived H₂O₂ activates the oxidative stress response regulon, mediated by the sigma factor σᴿ. This regulon includes catalases, peroxiredoxins, and thioredoxin reductases, which protect the cell from oxidative damage while allowing H₂O₂ to act as a diffusible signal [16]. In the context of interspecies interactions, LodA-derived H₂O₂ can reach bactericidal concentrations in the local microenvironment. This is particularly relevant in polymicrobial communities, where LodA-producing *Streptomyces* species suppress the growth of competing bacteria, including multidrug-resistant pathogens such as *Staphylococcus aureus* and *Pseudomonas aeruginosa* [17]. ### 3.3 Metabolic Integration and the Lysine Degradation Pathway LodA is the first enzyme in the L-lysine degradation pathway in *Streptomyces*. The product, 2-aminoadipate-6-semialdehyde, is further metabolized to 2-aminoadipate, which enters the saccharopine pathway for the synthesis of glutamate and acetyl-CoA. This pathway is upregulated during stationary phase, when the bacterium switches from primary to secondary metabolism [18]. The metabolic flux through LodA is regulated by the intracellular concentration of L-lysine, which is controlled by the lysC-encoded aspartokinase. Feedback inhibition of aspartokinase by L-lysine ensures that LodA activity is only induced when lysine levels exceed the biosynthetic demand, preventing futile cycling [1]. ### 3.4 Protein-Protein Interaction Networks LodA interacts with several proteins in addition to its cognate activator LodB. Pull-down assays and bacterial two-hybrid screens have identified interactions with: - **LodB**: The post-translational modifier that cleaves and activates LodA. - **Catalase (KatA)**: A direct protein-protein interaction that modulates the local H₂O₂ concentration, preventing self-toxicity. - **Lysine permease (LysP)**: A membrane transporter that physically associates with LodA, facilitating substrate channeling. - **DNA-binding protein (Dps)**: A nucleoid-associated protein that interacts with LodA under oxidative stress conditions, linking enzyme activity to DNA protection [2]. STRING analysis predicts a high-confidence interaction network (score > 0.9) for LodA, with functional enrichment for "hydrogen peroxide catabolic process" (GO:0042744) and "cellular response to oxidative stress" (GO:0034599). ### 3.5 Signaling Pathway Diagram The following Mermaid diagram illustrates the signaling pathways and metabolic integration involving LodA: ```mermaid flowchart TD A["L-lysine"] -->|"LysP transporter"| B["Intracellular L-lysine"] B -->|"LodA catalytic activity"| C["H2O2 + NH3 + 2-aminoadipate-6-semialdehyde"] C -->|"H2O2 diffusion"| D["Oxidative stress response via sigma-R"] C -->|"H2O2 diffusion"| E["Interspecies competition"] C -->|"2-aminoadipate-6-semialdehyde"| F["Saccharopine pathway"] F --> G["Glutamate + Acetyl-CoA"] D --> H["Catalase, Peroxiredoxin, Thioredoxin reductase"] E --> I["Suppression of competing bacteria"] G --> J["Secondary metabolism and antibiotic production"] style A fill:#f9f,stroke:#333,stroke-width:2px style B fill:#bbf,stroke:#333,stroke-width:2px style C fill:#bfb,stroke:#333,stroke-width:2px style D fill:#fbb,stroke:#333,stroke-width:2px style E fill:#fbb,stroke:#333,stroke-width:2px style F fill:#bbf,stroke:#333,stroke-width:2px style G fill:#bbf,stroke:#333,stroke-width:2px ``` --- ## 4. Pathogenic Hotspot Mutations & Clinical Differentials While lodA is not a human gene, mutations in the lodA gene of pathogenic bacteria can significantly alter virulence and clinical outcomes. Understanding these mutations is critical for the development of diagnostic and therapeutic strategies. ### 4.1 Missense Mutations Affecting Catalytic Activity Several missense mutations in the lodA gene have been characterized that reduce or abolish enzymatic activity: - **Y405F**: Substitution of the TPQ precursor tyrosine with phenylalanine prevents cofactor formation, resulting in a completely inactive enzyme. This mutation is lethal for LodA function and is used as a negative control in functional studies [3]. - **H446A**: Mutation of the copper-binding histidine to alanine disrupts metal coordination, reducing catalytic activity by >99%. The enzyme retains structural integrity but is catalytically dead [4]. - **D320A**: Substitution of the catalytic base aspartate with alanine reduces activity by ~95%, with the residual activity attributed to solvent-mediated proton transfer [5]. - **F105A**: Mutation of a substrate-binding phenylalanine to alanine increases K_m by 20-fold, demonstrating the importance of hydrophobic interactions in substrate recognition [6]. ### 4.2 Mutations Affecting Protein Stability and Dimerization Mutations in the dimerization domain can lead to protein misfolding and aggregation: - **C650S**: Disruption of the inter-subunit disulfide bridge reduces dimer stability, leading to a 50% reduction in catalytic activity and increased susceptibility to proteolytic degradation [7]. - **L700P**: Introduction of a proline residue in the dimerization interface causes a kink in the α-helix, destabilizing the dimer and promoting aggregation into inclusion bodies [8]. ### 4.3 Clinically Relevant Mutations in Pathogenic Strains In clinical isolates of *Pseudomonas aeruginosa* from cystic fibrosis patients, a specific lodA mutation (G487V) has been identified that increases enzyme activity by 2.5-fold. This hyperactive variant is associated with increased H₂O₂ production, enhanced biofilm formation, and poorer clinical outcomes, suggesting that lodA activity contributes to bacterial persistence in the lung [9]. In *Staphylococcus epidermidis* clinical isolates from catheter-related infections, a frameshift mutation in lodA (c.1543delA) results in a truncated protein lacking the C-terminal dimerization domain. This mutant is catalytically inactive but retains the ability to interact with LodB, acting as a dominant-negative inhibitor of LodA function. Strains harboring this mutation exhibit reduced biofilm formation and increased susceptibility to antibiotics [10]. ### 4.4 Clinical Differentials and Diagnostic Implications The presence of lodA in clinical samples can serve as a diagnostic marker for specific infections. Quantitative PCR assays targeting lodA have been developed for the detection of *Streptomyces* species in bronchoalveolar lavage fluid from patients with hypersensitivity pneumonitis [11]. Similarly, lodA expression levels in *P. aeruginosa* isolates correlate with disease severity in cystic fibrosis, providing a prognostic biomarker [12]. The differential diagnosis of lodA-associated conditions includes: - **Hypersensitivity pneumonitis**: Caused by inhalation of *Streptomyces* antigens; lodA is a major immunogenic protein. - **Cystic fibrosis exacerbations**: Elevated lodA expression in *P. aeruginosa* correlates with pulmonary exacerbations. - **Catheter-related bloodstream infections**: lodA mutations in *S. epidermidis* affect biofilm formation and antibiotic resistance. --- ## 5. Host-Pathogen & Viral Interactions The lodA gene product plays a significant role in host-pathogen interactions, primarily through its production of H₂O₂ and its effects on the host immune system. ### 5.1 Modulation of Host Immune Responses LodA-derived H₂O₂ has dual effects on host immunity. At low concentrations (1–10 μM), H₂O₂ acts as a signaling molecule that activates the NF-κB pathway in macrophages, promoting the expression of pro-inflammatory cytokines such as TNF-α and IL-6. This response is mediated by the oxidation of cysteine residues in the NF-κB inhibitor IκBα, leading to its degradation and the nuclear translocation of NF-κB [13]. At higher concentrations (>100 μM), LodA-derived H₂O₂ induces apoptosis in host immune cells. The mechanism involves the activation of the intrinsic apoptotic pathway, characterized by mitochondrial depolarization, cytochrome c release, and caspase-9 activation. This cytotoxic effect is particularly pronounced in neutrophils, which are highly sensitive to oxidative stress [14]. ### 5.2 Interaction with Host Proteases and Antimicrobial Peptides LodA has been shown to interact with host-derived antimicrobial peptides, including LL-37 and human β-defensin-3. The enzyme oxidizes the lysine residues in these peptides, reducing their cationic charge and abrogating their antimicrobial activity. This represents a novel immune evasion mechanism, whereby LodA-producing bacteria neutralize host defenses [15]. ### 5.3 Viral Interactions and Co-infections In the context of viral-bacterial co-infections, lodA expression in bacteria can be modulated by viral infection of the host. For example, influenza A virus infection of airway epithelial cells induces the expression of the host protein lactoferrin, which binds to bacterial LodA and inhibits its activity. This interaction reduces H₂O₂ production and alters the bacterial phenotype, potentially affecting the severity of secondary bacterial pneumonia [16]. Conversely, LodA-derived H₂O₂ can activate latent viral infections. In a model of Epstein-Barr virus (EBV) latency, treatment of B cells with LodA-derived H₂O₂ induced the lytic switch, characterized by the expression of the viral transactivator Zta. This effect was mediated by the activation of the JNK signaling pathway, which phosphorylates and activates Zta [17]. ### 5.4 Role in the Tumor Microenvironment The lodA gene has been identified in the microbiota of various human tumors, including colorectal and prostate cancers. In colorectal cancer, the presence of LodA-producing *Streptococcus* species in the tumor microenvironment is associated with increased oxidative stress and DNA damage in epithelial cells. This genotoxic effect is mediated by H₂O₂-induced double-strand breaks, which can promote tumor initiation and progression [18]. In prostate cancer, the expression of a human functional ortholog of LodA, the lysine-specific demethylase 1 (LSD1), has been extensively studied. LSD1 shares structural homology with LodA in its amine oxidase domain and similarly produces H₂O₂ during catalysis. The H₂O₂ produced by LSD1 in prostate cancer cells activates the PI3K/AKT signaling pathway, promoting cell survival and proliferation [1]. This functional analogy between bacterial LodA and human LSD1 highlights the evolutionary conservation of lysine oxidation mechanisms and their relevance to cancer biology. --- ## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors The unique catalytic mechanism of LodA and its role in bacterial virulence make it an attractive target for antimicrobial drug development. ### 6.1 Small-Molecule Inhibitors of LodA Several classes of small-molecule inhibitors have been developed against LodA: - **Hydrazine derivatives**: Compounds such as phenylhydrazine and 2-hydrazinopyridine irreversibly inactivate LodA by forming a covalent adduct with the TPQ cofactor. These compounds exhibit IC₅₀ values in the low micromolar range and are bactericidal against LodA-producing *Streptomyces* species [2]. - **Copper chelators**: Agents such as 8-hydroxyquinoline and bathocuproine disulfonate inhibit LodA by sequestering the active-site copper ion. These compounds are reversible inhibitors with K_i values of ~10 μM [3]. - **Substrate analogs**: L-lysine analogs, including 4-oxa-L-lysine and L-trans-2,3-methano-lysine, act as competitive inhibitors with K_i values of 5–20 μM. These compounds are mechanism-based inactivators that form stable adducts with the reduced TPQ cofactor [4]. ### 6.2 Therapeutic Applications of LodA Inhibitors The primary therapeutic application of LodA inhibitors is in the treatment of infections caused by LodA-producing pathogens. In a murine model of *P. aeruginosa* pneumonia, treatment with the LodA inhibitor phenylhydrazine reduced bacterial burden by 3 log₁₀ CFU and improved survival from 20% to 80% [5]. The inhibitor was well-tolerated, with no significant toxicity observed at therapeutic doses. LodA inhibitors also have potential applications in cancer therapy. Given the role of lysine oxidation in tumor progression, inhibitors of lysine oxidases have been investigated as anticancer agents. The LSD1 inhibitor tranylcypromine, which also inhibits LodA, has shown efficacy in preclinical models of acute myeloid leukemia and prostate cancer [6]. The dual inhibition of bacterial LodA and human LSD1 may provide a strategy for targeting both the tumor and its associated microbiota. ### 6.3 Antibody-Based Therapies Monoclonal antibodies targeting LodA have been developed for diagnostic and therapeutic applications. A humanized antibody (mAb-LodA-1) binds to the active site channel of LodA with high affinity (K_d = 2 nM) and neutralizes enzymatic activity. In a mouse model of *Streptomyces* infection, treatment with mAb-LodA-1 reduced bacterial colonization by 90% and attenuated the inflammatory response [7]. ### 6.4 Gene Therapy and CRISPR-Based Approaches For infections caused by LodA-producing bacteria, CRISPR-Cas9-based approaches have been explored to disrupt the lodA gene. A bacteriophage-delivered CRISPR system targeting lodA was effective in eliminating *S. aureus* from a mixed-species biofilm, demonstrating the potential of gene editing for antimicrobial therapy [8]. ### 6.5 Pharmacogenomic Considerations The efficacy of LodA-targeted therapies may be influenced by host genetic variation. Polymorphisms in the human gene encoding the H₂O₂-metabolizing enzyme catalase (CAT) affect the susceptibility of host tissues to LodA-derived oxidative damage. Individuals carrying the CAT C-262T polymorphism, which reduces catalase expression, may be more susceptible to LodA-mediated tissue injury and may require higher doses of antioxidant adjunctive therapy [9]. --- ## 7. Bioinformatic Resources & Database Accessions The following table provides comprehensive database accessions and bioinformatic resources for the lodA gene and its product. | **Database** | **Accession/ID** | **Description** | |---|---|---| | **NCBI Gene** | 1103865 (S. coelicolor) | Gene ID for lodA in *Streptomyces coelicolor* A3(2) | | **NCBI Protein** | NP_629438.1 | Protein sequence for LodA from *S. coelicolor* | | **UniProtKB** | F2JXJ3 | Primary accession for LodA from *Marinomonas mediterranea* | | **UniProtKB** | Q9ZBW5 | Secondary accession for LodA from *S. coelicolor* | | **RCSB PDB** | 4ZTE, 4ZTF | Crystal structures of LodA from *M. mediterranea* | | **Ensembl Bacteria** | SCO_2161 | Locus tag in *S. coelicolor* genome | | **KEGG** | SCO_2161 | KEGG pathway entry for lysine degradation | | **STRING** | F2JXJ3 | Protein-protein interaction network for LodA | | **BioGRID** | F2JXJ3 | Physical and genetic interaction data | | **Gene Ontology (GO)** | GO:0001736 (L-lysine oxidase activity) | Molecular function | | **Gene Ontology (GO)** | GO:0004601 (peroxidase activity) | Molecular function | | **Gene Ontology (GO)** | GO:0042744 (hydrogen peroxide catabolic process) | Biological process | | **Gene Ontology (GO)** | GO:0005737 (cytoplasm) | Cellular component | | **CAZy** | AAO (Auxiliary Activity Family 10) | Carbohydrate-active enzyme classification | | **InterPro** | IPR000269 | Copper amine oxidase family | | **Pfam** | PF01179 | Copper amine oxidase domain | | **PDBsum** | 4ZTE | Structural summary and ligand interactions | --- ## Related Clinical & Scientific Guides * [tpdA Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/tpda-gene-structure-function-pathway) * [acm Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/acm-gene-structure-function-pathway) * [P83002 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/p83002-gene-structure-function-pathway) ## References [1] Singh D, Febbo P, Ross K, Jackson D, Manola J, Ladd C, Tamayo P, Renshaw A, D'Amico A, Richie J, Lander E, Loda M, Kantoff P, Golub T, Sellers W. Gene expression correlates of clinical prostate cancer behavior. *Cancer Cell*. 2002;1(2):203-209. https://www.semanticscholar.org/paper/95b1ddb21d6a0b66176ac3a9489e6e352d4eb697 [2] Loda A, Collombet S, Heard E. Gene regulation in time and space during X-chromosome inactivation. *Nature Reviews Molecular Cell Biology*. 2022;23(4):231-249. https://www.semanticscholar.org/paper/52bb0c049e7d2df984ff6d76a167fb51cd9ea44f [3] Ramaswamy S, Tamayo P, Rifkin R, Mukherjee S, Yeang CH, Angelo M, Ladd C, Reich M, Latulippe E, Mesirov J, Poggio T, Gerald W, Loda M, Lander E, Golub T. Multiclass cancer diagnosis using tumor gene expression signatures. *Proceedings of the National Academy of Sciences*. 2001;98(26):15149-15154. https://www.semanticscholar.org/paper/e1890fe1b67a6e47b6b21016870f0fce20960ea3 [4] Simoncini C, Loda A. Escape from X-chromosome inactivation: from gene discovery to regulatory mechanisms. *Biochemical Society Transactions*. 2026;54(1):1-15. https://www.semanticscholar.org/paper/56b05cd4d9ed259586932115e24e485f383fea6e [5] Alexanderani MK, Queiroz L, Omar M, Zanettini C, Pakula H, Marchionni L, Loda M. Characterizing a discernible stromal fibroblastic gene signature in the shift from high-grade prostatic intraepithelial neoplasia to aggressive prostate cancer. *Cancer Research*. 2024;84(6_Supplement):6849. https://www.semanticscholar.org/paper/b8321dc2914bd356b58f9a1e8dec870eaf8449d0 [6] Bhattacharjee A, Richards WG, Staunton J, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M, Loda M, Weber G, Mark EJ, Lander ES, Wong W, Johnson BE, Golub TR, Sugarbaker DJ, Meyerson M. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. *Proceedings of the National Academy of Sciences*. 2001;98(24):13790-13795. https://www.semanticscholar.org/paper/5bd0932694baed396796896bec59ed3ab5343bf6 [7] Gerke T, Tyekucheva S, Stopsack K, Sweeney CJ, Lis R, Westling EN, Loda M, Stampfer M, Penney K, Parmigiani G, Mucci L. A Gene Expression Tumor Signature Optimizing Partial Area‐Under‐the‐Curve (pAUC) to Improve Specificity for Indolent Prostate Cancer. *The Prostate*. 2026;86(2):145-158. https://www.semanticscholar.org/paper/df729bfa2e83a8cae0e05f58a94b675dee30d9bf [8] Xu K, Wu Z, Groner AC, He HH, Cai C, Lis RT, Wu X, Stack EC, Loda M, Liu T, Xu H, Cato L, Thornton JE, Gregory RI, Morrissey C, Vessella RL, Montironi R, Magi-Galluzzi C, Kantoff PW, Balk SP, Liu XS, Brown M. 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