4.6 Article

Crystal Structure of the [4Fe-4S] Cluster-Containing Adenosine-5′-phosphosulfate Reductase from Mycobacterium tuberculosis

Journal

ACS OMEGA
Volume 6, Issue 21, Pages 13756-13765

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsomega.1c01043

Keywords

-

Funding

  1. National Institute of General Medical Sciences of the National Institutes of Health [R35 GM126982, R01 GM087638, P30 GM124165]
  2. DOE Office of Science [DE-AC02-06CH11357]

Ask authors/readers for more resources

Tuberculosis is the deadliest infectious disease in the world. APS reductase plays a vital role in producing essential reduced-sulfur-containing metabolites in Mycobacterium tuberculosis, making it a potential target for therapeutic interventions. The crystal structure of MtbAPSR provides important information for structure-based drug design aimed at combating TB.
Tuberculosis (TB) is the deadliest infectious disease in the world. In Mycobacterium tuberculosis, the first committed step in sulfate assimilation is the reductive cleavage of adenosine-5'-phosphosulfate (APS) to form adenosine-5'-phosphate (AMP) and sulfite by the enzyme APS reductase (APSR). The vital role of APSR in the production of essential reduced-sulfur-containing metabolites and the absence of a homologue enzyme in humans makes APSR a potential target for therapeutic interventions. Here, we present the crystal structure of the [4Fe-4S] cluster-containing APSR from M. tuberculosis (MtbAPSR) and compare it to previously determined structures of sulfonucleotide reductases. We further present MtbAPSR structures with substrate APS and product AMP bound in the active site. Our structures at a 3.1 angstrom resolution show high structural similarity to other sulfonucleotide reductases and reveal that APS and AMP have similar binding modes. These studies provide structural data for structure-based drug design aimed to combat TB.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available