Crystal structure of cystalysin from Treponema denticola: a pyridoxal 5′-phosphate-dependent protein acting as a haemolytic enzyme

• Published in: The EMBO journal 2000-07, Vol.19 (13), p.3168-3178
• Main Authors: Krupka, Heike I., Huber, Robert, Holt, Stanley C., Clausen, Tim
• Format: Article
• Language: English
• Subjects: Amino acids; aminoethoxyvinylglycine; Binding Sites; catalysin; Catalysis; Chemical reactions; Crystallography, X-Ray; Cystathionine gamma-Lyase - antagonists & inhibitors; Cystathionine gamma-Lyase - chemistry; Cystathionine gamma-Lyase - metabolism; cysteine desulfhydrase; Cytotoxicity; Enzymatic activity; Glycine - analogs & derivatives; Glycine - pharmacology; haemolysin; Hemolysin Proteins - chemistry; Hemolysin Proteins - drug effects; Hemolysin Proteins - metabolism; Hemolysis; Hydrogen sulfide; Hydrogen Sulfide - metabolism; Models, Molecular; periodontitis; protein crystallography; Protein Folding; pyridoxal 5'-phosphate; Pyridoxal Phosphate - metabolism; Sulfur - metabolism; Treponema - chemistry; Treponema denticola
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/19.13.3168

Cystalysin is a C β –S γ lyase from the oral pathogen Treponema denticola catabolyzing L ‐cysteine to produce pyruvate, ammonia and H 2 S. With its ability to induce cell lysis, cystalysin represents a new class of pyridoxal 5′‐phosphate (PLP)‐dependent virulence factors. The crystal structure of cystalysin was solved at 1.9 Å resolution and revealed a folding and quaternary arrangement similar to aminotransferases. Based on the active site architecture, a detailed catalytic mechanism is proposed for the catabolism of S‐containing amino acid substrates yielding H 2 S and cysteine persulfide. Since no homologies were observed with known haemolysins the cytotoxicity of cystalysin is attributed to this chemical reaction. Analysis of the cystalysin– L ‐aminoethoxyvinylglycine (AVG) complex revealed a ‘dead end’ ketimine PLP derivative, resulting in a total loss of enzyme activity. Cystalysin represents an essential factor of adult periodontitis, therefore the structure of the cystalysin–AVG complex may provide the chemical basis for rational drug design.