Dataset Information

Structural and functional studies of Spr1654: an essential aminotransferase in teichoic acid biosynthesis in Streptococcus pneumoniae.

ABSTRACT: Spr1654 from Streptococcus pneumoniae plays a key role in the production of unusual sugars, presumably functioning as a pyridoxal-5'-phosphate (PLP)-dependent aminotransferase. Spr1654 was predicted to catalyse the transferring of amino group to form the amino sugar 2-acetamido-4-amino-2, 4, 6-trideoxygalactose moiety (AATGal), representing a crucial step in biosynthesis of teichoic acids in S. pneumoniae We have determined the crystal structures of the apo-, PLP- and PMP-bound forms of Spr1654. Spr1654 forms a homodimer, in which each monomer contains one active site. Using spectrophotometry and based on absorbance profiles of PLP- and PMP-formed enzymes, our results indicate that l-glutamate is most likely the preferred amino donor. Structural superposition of the crystal structures of Spr1654 on previously determined structures of other sugar aminotransferases in complex with glutamate and/or UDP-activated sugar allowed us to identify key Spr1654 residues for ligand binding and catalysis. The crystal structures of Spr1654 and in complex with PLP and PMP can direct the future rational design of novel therapeutic compounds against S. pneumoniae.

SUBMITTER: Han X

PROVIDER: S-EPMC5936713 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Structural and functional studies of Spr1654: an essential aminotransferase in teichoic acid biosynthesis in Streptococcus pneumoniae.

Han Xiao X Sun Renhua R Sandalova Tatyana T Achour Adnane A

Open biology 20180401 4

Spr1654 from Streptococcus pneumoniae plays a key role in the production of unusual sugars, presumably functioning as a pyridoxal-5'-phosphate (PLP)-dependent aminotransferase. Spr1654 was predicted to catalyse the transferring of amino group to form the amino sugar 2-acetamido-4-amino-2, 4, 6-trideoxygalactose moiety (AATGal), representing a crucial step in biosynthesis of teichoic acids in S. pneumoniae We have determined the crystal structures of the apo-, PLP- and PMP-bound for ...[more]

PMID: 29669826

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Project description:ABSTRACT The major clonal lineages of the human pathogen Staphylococcus aureus produce cell wall-anchored anionic poly-ribitol-phosphate (RboP) wall teichoic acids (WTA) substituted with d-Alanine and N-acetyl-d-glucosamine. The phylogenetically isolated S. aureus ST395 lineage has recently been found to produce a unique poly-glycerol-phosphate (GroP) WTA glycosylated with N-acetyl-d-galactosamine (GalNAc). ST395 clones bear putative WTA biosynthesis genes on a novel genetic element probably acquired from coagulase-negative staphylococci (CoNS). We elucidated the ST395 WTA biosynthesis pathway and identified three novel WTA biosynthetic genes, including those encoding an ?-O-GalNAc transferase TagN, a nucleotide sugar epimerase TagV probably required for generation of the activated sugar donor substrate for TagN, and an unusually short GroP WTA polymerase TagF. By using a panel of mutants derived from ST395, the GalNAc residues carried by GroP WTA were found to be required for infection by the ST395-specific bacteriophage ?187 and to play a crucial role in horizontal gene transfer of S. aureus pathogenicity islands (SaPIs). Notably, ectopic expression of ST395 WTA biosynthesis genes rendered normal S. aureus susceptible to ?187 and enabled ?187-mediated SaPI transfer from ST395 to regular S. aureus. We provide evidence that exchange of WTA genes and their combination in variable, mosaic-like gene clusters have shaped the evolution of staphylococci and their capacities to undergo horizontal gene transfer events. IMPORTANCE The structural highly diverse wall teichoic acids (WTA) are cell wall-anchored glycopolymers produced by most Gram-positive bacteria. While most of the dominant Staphylococcus aureus lineages produce poly-ribitol-phosphate WTA, the recently described ST395 lineage produces a distinct poly-glycerol-phosphate WTA type resembling the WTA backbone of coagulase-negative staphylococci (CoNS). Here, we analyzed the ST395 WTA biosynthesis pathway and found new types of WTA biosynthesis genes along with an evolutionary link between ST395 and CoNS, from which the ST395 WTA genes probably originate. The elucidation of ST395 WTA biosynthesis will help to understand how Gram-positive bacteria produce highly variable WTA types and elucidate functional consequences of WTA variation.

Dataset Information

Structural and functional studies of Spr1654: an essential aminotransferase in teichoic acid biosynthesis in Streptococcus pneumoniae.

Publications

Structural and functional studies of Spr1654: an essential aminotransferase in teichoic acid biosynthesis in <i>Streptococcus pneumoniae</i>.

Similar Datasets

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