7LHU

Crystal structure of adenosine-5'-phosphosulfate reductase from Mycobacterium tuberculosis in a complex with product AMP

Summary for 7LHU

• Entry DOI: 10.2210/pdb7lhu/pdb
• Related: 7LHR 7LHS
• Descriptor: Phosphoadenosine phosphosulfate reductase, IRON/SULFUR CLUSTER, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total)
• Functional Keywords: amp, adenosine-5'-phosphosulfate reductase, tuberculosis, oxidoreductase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 58838.33

Authors

Feliciano, P.R.,Drennan, C.L. (deposition date: 2021-01-26, release date: 2021-07-07, Last modification date: 2023-10-18)

Primary citation

Feliciano, P.R.,Carroll, K.S.,Drennan, C.L.
Crystal Structure of the [4Fe-4S] Cluster-Containing Adenosine-5'-phosphosulfate Reductase from Mycobacterium tuberculosis .
Acs Omega, 6:13756-13765, 2021

PubMed Abstract: Tuberculosis (TB) is the deadliest infectious disease in the world. In , 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 (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 Å 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.

PubMed: 34095667
DOI: 10.1021/acsomega.1c01043

Experimental method

X-RAY DIFFRACTION (3.09 Å)