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NIAID Structure of the Month

Clostridium difficile: enzyme 3-dehydroquinate dehydratase

The February Structure of the Month comes from Clostridium difficile, which is the most serious cause of antibiotic-associated diarrhea in humans and can lead to pseudomembranous colitis, a severe infection of the colon often resulting from eradication of the normal gut flora by antibiotics.

C. diff enzyme structure
The enzyme 3-dehydroquinate dehydratase structure was determined by the Center for Structural Genomics of Infectious Diseases (CSGID).

 

The depicted structure represents the enzyme 3-dehydroquinate dehydratase in the shikimate pathway. This enzyme is vital for most bacteria and plants but absent in animals. 3-dehydroquinate dehydratases are attractive targets for the development of novel antibiotics.

The figure represents the structure (in the presence of substrate, PDB code: 3JS3, in purple), superimposed on the structure of the same enzyme from Salmonella enterica (in the absence of substrate, PDB code: 3L2I, in pink). Note how a flexible loop of the enzyme becomes ordered and covers the active site when the substrate is bound (in dark purple labeled as “Closed LID”) or it is otherwise disordered in the absence of substrate (in deep pink labeled as “Disordered LID”).

Both structures have been determined by the Center for Structural Genomics of Infectious Diseases (CSGID) . For more information please click see:

  • structure from Clostridium difficile, IDP90163
  • structure from Salmonella enterica, IDP90922.

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Last Updated March 02, 2011