Skip to main content

Structural studies on Mycobacterium tuberculosis DXR in complex with the antibiotic FR‐900098

Buy Article:

$51.00 plus tax (Refund Policy)


A number of pathogens, including the causative agents of tuberculosis and malaria, synthesize the essential isoprenoid precursor isopentenyl diphosphate via the 2‐C‐methyl‐d‐erythritol 4‐phosphate (MEP) pathway rather than the classical mevalonate pathway that is found in humans. As part of a structure‐based drug‐discovery program against tuberculosis, DXR, the enzyme that carries out the second step in the MEP pathway, has been investigated. This enzyme is the target for the antibiotic fosmidomycin and its active acetyl derivative FR‐900098. The structure of DXR from Mycobacterium tuberculosis in complex with FR‐900098, manganese and the NADPH cofactor has been solved and refined. This is a new crystal form that diffracts to a higher resolution than any other DXR complex reported to date. Comparisons with other ternary complexes show that the conformation is that of the enzyme in an active state: the active‐site flap is well defined and the cofactor‐binding domain has a conformation that brings the NADPH into the active site in a manner suitable for catalysis. The substrate‐binding site is highly conserved in a number of pathogens that use this pathway, so any new inhibitor that is designed for the M. tuberculosis enzyme is likely to exhibit broad‐spectrum activity.

Document Type: Research Article


Affiliations: Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden

Publication date: February 1, 2012

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Partial Open Access Content
Partial Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more