PDBsum entry 2mmt

Antibiotic

PDB id: 2mmt

Contents

Protein chain

21 a.a.

PDB id:

2mmt

Name:

Antibiotic

Title:

Lasso peptide-based integrin inhibitor: microcin j25 variant with rgdf substitution of gly12-ile13-gly14-thr15

Structure:

Microcin j25 rgdf mutant. Chain: a. Fragment: unp residues 38-58. Synonym: mccj25(rgdf). Engineered: yes. Mutation: yes

Source:

Synthetic: yes. Escherichia coli. Organism_taxid: 562

NMR struc:

15 models

Authors:

J.D.Hegemann,M.Zimmermann,T.A.Knappe,X.Xie,M.A.Marahiel

Key ref:

J.D.Hegemann et al. (2014). Rational improvement of the affinity and selectivity of integrin binding of grafted lasso peptides. J Med Chem, 57, 5829-5834. PubMed id: 24949551 DOI: 10.1021/jm5004478

Date:

18-Mar-14 Release date: 02-Jul-14

Protein chain

Q9X2V7  (MCJA_ECOLX) -  Microcin J25 from Escherichia coli

Seq: 58 a.a.

Struc: 21 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1021/jm5004478

J Med Chem 57:5829-5834 (2014)

PubMed id: 24949551

Rational improvement of the affinity and selectivity of integrin binding of grafted lasso peptides.

J.D.Hegemann, M.De Simone, M.Zimmermann, T.A.Knappe, X.Xie, F.S.Di Leva, L.Marinelli, E.Novellino, S.Zahler, H.Kessler, M.A.Marahiel.

ABSTRACT

Integrins moderate diverse important functions in the human body and are promising targets in cancer therapy. Hence, the selective inhibition of specific integrins is of great medicinal interest. Here, we report the optimization of a grafted lasso peptide, yielding MccJ25(RGDF), which is a highly potent and selective αvβ3 integrin inhibitor. Furthermore, its NMR structure was elucidated and employed in a molecular dynamics approach, revealing information about the integrin binding mode and selectivity profile of MccJ25(RGDF).