PDBsum entry 4v1v

Hydrolase

PDB id: 4v1v

Contents

Protein chains

747 a.a.

14 a.a.

13 a.a.

Ligands

ANP ×2

Metals

_MG ×4

_ZN ×2

PDB id:

4v1v

Name:

Hydrolase

Title:

Heterocyclase in complex with substrate and cofactor

Structure:

Lynd. Chain: a, b. Engineered: yes. Lynd. Chain: c, d. Engineered: yes

Source:

Lyngbya aestuarii. Organism_taxid: 118322. Expressed in: escherichia coli. Expression_system_taxid: 511693. Uncultured prochloron sp.. Organism_taxid: 259942.

Resolution:

3.01Å R-factor: 0.214 R-free: 0.266

Authors:

J.Koehnke,J.H.Naismith

Key ref:

J.Koehnke et al. (2015). Structural analysis of leader peptide binding enables leader-free cyanobactin processing. Nat Chem Biol, 11, 558-563. PubMed id: 26098679 DOI: 10.1038/nchembio.1841

Date:

02-Oct-14 Release date: 14-Jan-15

Protein chains

A0YXD2  (A0YXD2_LYNSP) -  YcaO domain-containing protein from Lyngbya sp. (strain PCC 8106)

Seq: 775 a.a.

Struc: 747 a.a.

Protein chain

A0MHA3  (A0MHA3_9PROC) -  Patellamide protein from uncultured Prochloron sp

Seq: 71 a.a.

Struc: 14 a.a.

Protein chain

A0MHA3  (A0MHA3_9PROC) -  Patellamide protein from uncultured Prochloron sp

Seq: 71 a.a.

Struc: 13 a.a.

DOI no: 10.1038/nchembio.1841

Nat Chem Biol 11:558-563 (2015)

PubMed id: 26098679

Structural analysis of leader peptide binding enables leader-free cyanobactin processing.

J.Koehnke, G.Mann, A.F.Bent, H.Ludewig, S.Shirran, C.Botting, T.Lebl, W.E.Houssen, M.Jaspars, J.H.Naismith.

ABSTRACT

Regioselective modification of amino acids within the context of a peptide is common to a number of biosynthetic pathways, and many of the resulting products have potential as therapeutics. The ATP-dependent enzyme LynD heterocyclizes multiple cysteine residues to thiazolines within a peptide substrate. The enzyme requires the substrate to have a conserved N-terminal leader for full activity. Catalysis is almost insensitive to immediately flanking residues in the substrate, suggesting that recognition occurs distant from the active site. Nucleotide and peptide substrate co-complex structures of LynD reveal that the substrate leader peptide binds to and extends the β-sheet of a conserved domain of LynD, whereas catalysis is accomplished in another conserved domain. The spatial segregation of catalysis from recognition combines seemingly contradictory properties of regioselectivity and promiscuity, and it appears to be a conserved strategy in other peptide-modifying enzymes. A variant of LynD that efficiently processes substrates without a leader peptide has been engineered.