Structural highlights
6g59 is a 2 chain structure with sequence from Staam. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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Ligands: | , , , |
Gene: | alr1, alr, SAV2070 (STAAM) |
Activity: | Alanine racemase, with EC number 5.1.1.1 |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ALR1_STAAM] Catalyzes the interconversion of L-alanine and D-alanine.[1]
Publication Abstract from PubMed
Pyridoxal phosphate (PLP) is an enzyme cofactor required for the chemical transformation of biological amines in many central cellular processes. PLP-dependent enzymes (PLP-DEs) are ubiquitous and evolutionarily diverse, making their classification based on sequence homology challenging. Here we present a chemical proteomic method for reporting on PLP-DEs using functionalized cofactor probes. We synthesized pyridoxal analogues modified at the 2'-position, which are taken up by cells and metabolized in situ. These pyridoxal analogues are phosphorylated to functional cofactor surrogates by cellular pyridoxal kinases and bind to PLP-DEs via an aldimine bond which can be rendered irreversible by NaBH4 reduction. Conjugation to a reporter tag enables the subsequent identification of PLP-DEs using quantitative, label-free mass spectrometry. Using these probes we accessed a significant portion of the Staphylococcus aureus PLP-DE proteome (73%) and annotate uncharacterized proteins as novel PLP-DEs. We also show that this approach can be used to study structural tolerance within PLP-DE active sites and to screen for off-targets of the PLP-DE inhibitor D-cycloserine.
Mining the cellular inventory of pyridoxal phosphate-dependent enzymes with functionalized cofactor mimics.,Hoegl A, Nodwell MB, Kirsch VC, Bach NC, Pfanzelt M, Stahl M, Schneider S, Sieber SA Nat Chem. 2018 Oct 8. pii: 10.1038/s41557-018-0144-2. doi:, 10.1038/s41557-018-0144-2. PMID:30297752[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Scaletti ER, Luckner SR, Krause KL. Structural features and kinetic characterization of alanine racemase from Staphylococcus aureus (Mu50). Acta Crystallogr D Biol Crystallogr. 2012 Jan;68(Pt 1):82-92. Epub 2011 Dec 9. PMID:22194336 doi:10.1107/S0907444911050682
- ↑ Hoegl A, Nodwell MB, Kirsch VC, Bach NC, Pfanzelt M, Stahl M, Schneider S, Sieber SA. Mining the cellular inventory of pyridoxal phosphate-dependent enzymes with functionalized cofactor mimics. Nat Chem. 2018 Oct 8. pii: 10.1038/s41557-018-0144-2. doi:, 10.1038/s41557-018-0144-2. PMID:30297752 doi:http://dx.doi.org/10.1038/s41557-018-0144-2