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6r1n

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Crystal structure of S. aureus seryl-tRNA synthetase complexed to seryl sulfamoyl adenosine

Structural highlights

6r1n is a 1 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.03Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SYS_STAA8 Catalyzes the attachment of serine to tRNA(Ser). Is also probably able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec).^[1]

Publication Abstract from PubMed

Aminoacyl-tRNA synthetases are ubiquitous and essential enzymes for protein synthesis and also a variety of other metabolic processes, especially in bacterial species. Bacterial aminoacyl-tRNA synthetases represent attractive and validated targets for antimicrobial drug discovery if issues of prokaryotic versus eukaryotic selectivity and antibiotic resistance generation can be addressed. We have determined high-resolution X-ray crystal structures of the Escherichia coli and Staphylococcus aureus seryl-tRNA synthetases in complex with aminoacyl adenylate analogues and applied a structure-based drug discovery approach to explore and identify a series of small molecule inhibitors that selectively inhibit bacterial seryl-tRNA synthetases with greater than 2 orders of magnitude compared to their human homologue, demonstrating a route to the selective chemical inhibition of these bacterial targets.

Structure-Guided Enhancement of Selectivity of Chemical Probe Inhibitors Targeting Bacterial Seryl-tRNA Synthetase.,Cain R, Salimraj R, Punekar AS, Bellini D, Fishwick CWG, Czaplewski L, Scott DJ, Harris G, Dowson CG, Lloyd AJ, Roper DI J Med Chem. 2019 Nov 14;62(21):9703-9717. doi: 10.1021/acs.jmedchem.9b01131. Epub, 2019 Nov 5. PMID:31626547^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bausch N, Seignovert L, Beaulande M, Leberman R, Härtlein M. Analysis and overexpression in Escherichia coli of a staphylococcal gene encoding seryl-tRNA synthetase. Biochim Biophys Acta. 1998 Apr 29;1397(2):169-74. PMID:9565680 doi:10.1016/s0167-4781(98)00027-x
↑ Cain R, Salimraj R, Punekar AS, Bellini D, Fishwick CWG, Czaplewski L, Scott DJ, Harris G, Dowson CG, Lloyd AJ, Roper DI. Structure-Guided Enhancement of Selectivity of Chemical Probe Inhibitors Targeting Bacterial Seryl-tRNA Synthetase. J Med Chem. 2019 Nov 14;62(21):9703-9717. doi: 10.1021/acs.jmedchem.9b01131. Epub, 2019 Nov 5. PMID:31626547 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b01131