Structural and functional studies of Spr1654: an essential aminotransferase in teichoic acid biosynthesis in Streptococcus pneumoniae
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-tride...
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2018-04-01
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doaj-65a14a85207d4b75b7c6ac316165d7012020-11-25T03:51:59ZengThe Royal SocietyOpen Biology2046-24412018-04-018410.1098/rsob.170248170248Structural and functional studies of Spr1654: an essential aminotransferase in teichoic acid biosynthesis in Streptococcus pneumoniaeXiao HanRenhua SunTatyana SandalovaAdnane AchourSpr1654 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.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170248teichoic acidsaminotransferase spr1654plpl-glutamatecrystal structuresubstrate specificity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiao Han Renhua Sun Tatyana Sandalova Adnane Achour |
spellingShingle |
Xiao Han Renhua Sun Tatyana Sandalova Adnane Achour Structural and functional studies of Spr1654: an essential aminotransferase in teichoic acid biosynthesis in Streptococcus pneumoniae Open Biology teichoic acids aminotransferase spr1654 plp l-glutamate crystal structure substrate specificity |
author_facet |
Xiao Han Renhua Sun Tatyana Sandalova Adnane Achour |
author_sort |
Xiao Han |
title |
Structural and functional studies of Spr1654: an essential aminotransferase in teichoic acid biosynthesis in Streptococcus pneumoniae |
title_short |
Structural and functional studies of Spr1654: an essential aminotransferase in teichoic acid biosynthesis in Streptococcus pneumoniae |
title_full |
Structural and functional studies of Spr1654: an essential aminotransferase in teichoic acid biosynthesis in Streptococcus pneumoniae |
title_fullStr |
Structural and functional studies of Spr1654: an essential aminotransferase in teichoic acid biosynthesis in Streptococcus pneumoniae |
title_full_unstemmed |
Structural and functional studies of Spr1654: an essential aminotransferase in teichoic acid biosynthesis in Streptococcus pneumoniae |
title_sort |
structural and functional studies of spr1654: an essential aminotransferase in teichoic acid biosynthesis in streptococcus pneumoniae |
publisher |
The Royal Society |
series |
Open Biology |
issn |
2046-2441 |
publishDate |
2018-04-01 |
description |
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. |
topic |
teichoic acids aminotransferase spr1654 plp l-glutamate crystal structure substrate specificity |
url |
https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170248 |
work_keys_str_mv |
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