The Enzyme Database

Your query returned 1 entry.    printer_iconPrintable version

EC 6.2.2.3     
Accepted name: thiazoline synthase
Reaction: ATP + a [protein]-(L-amino acyl-L-cysteine) = ADP + phosphate + a [protein]-(1S,4R)-2-(C-substituted-aminomethyl)-4-acyl-2-thiazoline
Glossary: L-cysteine heterocyclase; truD (gene name); lynD (gene name)
Systematic name: [protein]-(L-amino acyl-L-cysteine) cyclodehydratase (2-thiazoline-forming)
Comments: Requires Mg2+. The enzyme, which participates in the biosynthesis of some ribosomal peptide natural products (RiPPs) such as the trunkamides, converts L-cysteine residues to thiazoline rings. The enzyme requires two domains - a cyclodehydratase domain, known as a YcaO domain, and a substrate recognition domain (RRE domain) that controls the regiospecificity of the enzyme. The RRE domain can either be fused to the YcaO domain or occur as a separate protein; however both domains are required for activity. The enzyme can process multiple L-cysteine residues within the same substrate peptide, and all enzymes characterized so far follow a defined order, starting with the L-cysteine closest to the C-terminus. The reaction involves phosphorylation of the preceding ribosomal peptide backbone amide bond, forming ADP and a phosphorylated intermediate, followed by release of the phosphate group. In some cases the enzyme catalyses a side reaction in which the phosphorylated intermediate reacts with ADP to form AMP and diphosphate. This activity is also catalysed by the related enzyme EC 6.2.2.2, oxazoline synthase. That enzyme differs by having an RRE domain that also recognizes L-serine and L-threonine residues, which are converted to oxazoline and methyloxazoline rings, respectively.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  McIntosh, J.A. and Schmidt, E.W. Marine molecular machines: heterocyclization in cyanobactin biosynthesis. ChemBioChem 11 (2010) 1413–1421. [PMID: 20540059]
2.  McIntosh, J.A., Donia, M.S. and Schmidt, E.W. Insights into heterocyclization from two highly similar enzymes. J. Am. Chem. Soc. 132 (2010) 4089–4091. [PMID: 20210311]
3.  Koehnke, J., Bent, A.F., Zollman, D., Smith, K., Houssen, W.E., Zhu, X., Mann, G., Lebl, T., Scharff, R., Shirran, S., Botting, C.H., Jaspars, M., Schwarz-Linek, U. and Naismith, J.H. The cyanobactin heterocyclase enzyme: a processive adenylase that operates with a defined order of reaction. Angew. Chem. Int. Ed. Engl. 52 (2013) 13991–13996. [PMID: 24214017]
4.  Koehnke, J., Mann, G., Bent, A.F., Ludewig, H., Shirran, S., Botting, C., Lebl, T., Houssen, W., Jaspars, M. and Naismith, J.H. Structural analysis of leader peptide binding enables leader-free cyanobactin processing. Nat. Chem. Biol. 11 (2015) 558–563. [PMID: 26098679]
5.  Ge, Y., Czekster, C.M., Miller, O.K., Botting, C.H., Schwarz-Linek, U. and Naismith, J.H. Insights into the mechanism of the cyanobactin heterocyclase enzyme. Biochemistry 58 (2019) 2125–2132. [PMID: 30912640]
[EC 6.2.2.3 created 2020]
 
 


Data © 2001–2021 IUBMB
Web site © 2005–2021 Andrew McDonald