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.
Specify your search results
The enzyme appears in viruses and cellular organisms
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.
in the absence of peptide substrate, LynD is likely catalyzing solely ATP hydrolysis to ADP and then to AMP, while in the presence of substrate, ATP consumption is coupled to heterocyclization. Presence of ATP is required for catalysis. ATP analogue AMP-CPP supports catalysis, while AMP-PCP does not
reaction mechanism, the gamma-phosphate of ATP is transferred in a kinase mechanism to the substrate to yield a phosphorylated intermediate common to all YcaO domain proteins. In cyanobactin heterocyclases, this phosphorylated intermediate, in a proportion of turnovers, reacts with ADP to yield AMP and diphosphate
the enzyme requires the substrate to have conserved N-terminal leader for full activity. The substrate leader peptide binds to and extends the beta sheet of a conserved domain of LynD, whilst catalysis is accomplished in another conserved domain. ATP binds in the conserved YcaO domain
to 2.9 A resolution. TruD can be decomposed into three domains (domain 1 residues 2-85, domain 2 residues 86-321, domain 3 residues 323-781), which combine to form an extended, curved molecule that exists as a dimer
a LynD fusion enzyme is produced by adding residues 21-38 of the PatE leader and an eleven residue long linker to the N-terminus of LynD. The fusion protein is active at processing two cysteines within a short test peptide ITACITFCAYDG and does not require a leader
6.2.2.3 thiazoline synthase
more
top
