4ffa

Sulfatase from Mycobacterium tuberculosisSulfatase from Mycobacterium tuberculosis

Structural highlights 4ffa is a 4 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ATSK_MYCTU Alpha-ketoglutarate-dependent sulfate ester dioxygenase, which oxidizes medium-chain alkyl-sulfate esters (PubMed:23762287). Shows preference for 2-ethylhexyl sulfate (2-EHS) in vitro, leading to the formation of succinate and 2-ethylhexanal (PubMed:23762287, PubMed:25427196). Has likely a role in sulfate scavenging in vivo (PubMed:23762287). Also causes the inactivation of the 2-carboxyquinoxaline Ty38c (an antitubercular compound that inhibits DprE1) via oxidative decarboxylation, using Ty38c instead of alpha-ketoglutarate as a substrate. Is thus responsible for primary resistance of M.tuberculosis to Ty38c in vitro. Overexpression of Rv3406 causes resistance to Ty38c. Publication Abstract from PubMed The genome of Mycobacterium tuberculosis (Mtb) encodes nine putative sulfatases, none of which have a known function or substrate. Here, we characterize Mtb's single putative type II sulfatase, Rv3406, as a non-heme iron (II) and alpha-ketoglutarate-dependent dioxygenase that catalyzes the oxidation and subsequent cleavage of alkyl sulfate esters. Rv3406 was identified based on its homology to the alkyl sulfatase AtsK from Pseudomonas putida. Using an in vitro biochemical assay, we confirmed that Rv3406 is a sulfatase with a preference for alkyl sulfate substrates similar to those processed by AtsK. We determined the crystal structure of the apo Rv3406 sulfatase at 2.5 A. The active site residues of Rv3406 and AtsK are essentially superimposable, suggesting that the two sulfatases share the same catalytic mechanism. Finally, we generated an Rv3406 mutant (Deltarv3406) in Mtb to study the sulfatase's role in sulfate scavenging. The Deltarv3406 strain did not replicate in minimal media with 2-ethyl hexyl sulfate as the sole sulfur source, in contrast to wild type Mtb or the complemented strain. We conclude that Rv3406 is an iron and alpha-ketoglutarate-dependent sulfate ester dioxygenase that has unique substrate specificity that is likely distinct from other Mtb sulfatases. Mycobacterium tuberculosis Rv3406 Is a Type II Alkyl Sulfatase Capable of Sulfate Scavenging.,Sogi KM, Gartner ZJ, Breidenbach MA, Appel MJ, Schelle MW, Bertozzi CR PLoS One. 2013 Jun 6;8(6):e65080. doi: 10.1371/journal.pone.0065080. Print 2013. PMID:23762287 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Sulfatase 3D structures

spinqualitylabelsall models 4ffa, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image