Recombinant Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai Gamma-glutamyl phosphate reductase (proA)
Description
Introduction to Gamma-Glutamyl Phosphate Reductase (ProA)
Gamma-glutamyl phosphate reductase (ProA) is an NADP-dependent enzyme (EC 1.2.1.41) that catalyzes the second step in proline biosynthesis, reducing L-glutamate 5-phosphate to L-glutamate 5-semialdehyde. This enzyme is critical for bacterial metabolism, particularly under stress conditions where proline serves as an osmoprotectant and energy source . In Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai, ProA is encoded by the proA gene, part of a conserved pathway for amino acid biosynthesis .
Role in Pathogenicity
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In R. solanacearum, ProA is essential for proline synthesis and regulates the type III secretion system (T3SS), a virulence determinant. proA mutants showed reduced T3SS expression and impaired colonization of host plants .
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Proline supplementation restored T3SS activity, suggesting ProA indirectly influences virulence via metabolic regulation .
Enzymatic Characteristics
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Catalytic Mechanism: ProA requires NADP as a cofactor and is inhibited by divalent cations like Cu²⁺ .
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Structural Insights: While Leptospira ProA’s structure remains uncharacterized, homologs like LiGAPDH (another metabolic enzyme) exhibit NAD⁺-binding domains and host immune evasion properties .
Metabolic Adaptations
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Leptospira alters outer membrane protein (OMP) expression under host-mimicking conditions, downregulating major OMPs like LipL32 to evade immune detection . ProA’s role in sustaining metabolic flexibility during infection warrants investigation.
Therapeutic and Diagnostic Targets
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Drug Development: Natural inhibitors like anacardic acid and curcumin inhibit bacterial GAPDH , suggesting similar strategies could target ProA.
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Vaccine Design: Recombinant OMPs (e.g., LipL41, OmpL1) are immunogenic in leptospirosis . ProA’s surface accessibility (predicted via secretion systems ) may make it a candidate for subunit vaccines.
Research Gaps and Future Directions
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Functional Studies: No direct data on L. interrogans ProA’s enzymatic activity or immune interactions exist in the reviewed literature.
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Structural Biology: Solving ProA’s crystal structure would aid in inhibitor design.
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In Vivo Validation: Assessing proA knockout strains in animal models could clarify its role in virulence.
Product Specs
Target Background
KEGG: lil:LA_0854
STRING: 189518.LA_0854
