Show simple item record

dc.contributor.authorCross, Megan
dc.contributor.authorLepage, Romain
dc.contributor.authorRajan, Siji
dc.contributor.authorBiberacher, Sonja
dc.contributor.authorYoung, Neil D
dc.contributor.authorKim, Bo-Na
dc.contributor.authorCoster, Mark J
dc.contributor.authorGasser, Robin B
dc.contributor.authorKim, Jeong-Sun
dc.contributor.authorHofmann, Andreas
dc.date.accessioned2017-12-14T01:39:50Z
dc.date.available2017-12-14T01:39:50Z
dc.date.issued2017
dc.identifier.issn0892-6638
dc.identifier.doi10.1096/fj.201601149R
dc.identifier.urihttp://hdl.handle.net/10072/100927
dc.description.abstractThe trehalose biosynthetic pathway is of great interest for the development of novel therapeutics because trehalose is an essential disaccharide in many pathogens but is neither required nor synthesized in mammalian hosts. As such, trehalose-6-phosphate phosphatase (TPP), a key enzyme in trehalose biosynthesis, is likely an attractive target for novel chemotherapeutics. Based on a survey of genomes from a panel of parasitic nematodes and bacterial organisms and by way of a structure-based amino acid sequence alignment, we derive the topological structure of monoenzyme TPPs and classify them into 3 groups. Comparison of the functional roles of amino acid residues located in the active site for TPPs belonging to different groups reveal nuanced variations. Because current literature on this enzyme family shows a tendency to infer functional roles for individual amino acid residues, we investigated the roles of the strictly conserved aspartate tetrad in TPPs of the nematode Brugia malayi by using a conservative mutation approach. In contrast to aspartate-213, the residue inferred to carry out the nucleophilic attack on the substrate, we found that aspartate-215 and aspartate-428 of BmTPP are involved in the chemistry steps of enzymatic hydrolysis of the substrate. Therefore, we suggest that homology-based inference of functionally important amino acids by sequence comparison for monoenzyme TPPs should only be carried out for each of the 3 groups.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherFederation of American Societies for Experimental Biology
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto12
dc.relation.ispartofjournalFASEB Journal
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchZoology
dc.subject.fieldofresearchMedical parasitology
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3109
dc.subject.fieldofresearchcode320704
dc.subject.fieldofresearchcode3208
dc.titleProbing function and structure of trehalose-6-phosphate phosphatases from pathogenic organisms suggests distinct molecular groupings
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Sciences, Griffith Institute for Drug Discovery
gro.description.notepublicThis publication has been entered into Griffith Research Online as an Advanced Online Version.
gro.hasfulltextNo Full Text
gro.griffith.authorCoster, Mark J.
gro.griffith.authorHofmann, Andreas
gro.griffith.authorLepage, Romain
gro.griffith.authorCross, Megan O.
gro.griffith.authorBiberacher, Sonja M.
gro.griffith.authorRajan, Siji


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record