2M7I
Solution structure of a Beta-Hairpin Peptidomimetic antibiotic that targets LptD in Pseudomonas sp.
Summary for 2M7I
Entry DOI | 10.2210/pdb2m7i/pdb |
Related | 2M7J |
NMR Information | BMRB: 19190 |
Related PRD ID | PRD_001063 |
Descriptor | Beta-Hairpin Peptidomimetic antibiotic TWL(DAB)(ORN)(DLY)RW(ORN)(DAB)AK(DPR)P (1 entity in total) |
Functional Keywords | peptidomimetics, beta-hairpin, antibiotic |
Total number of polymer chains | 1 |
Total formula weight | 1713.08 |
Authors | Moehle, K.,Schmidt, J.,Robinson, J. (deposition date: 2013-04-24, release date: 2013-09-11, Last modification date: 2023-06-14) |
Primary citation | Schmidt, J.,Patora-Komisarska, K.,Moehle, K.,Obrecht, D.,Robinson, J.A. Structural studies of beta-hairpin peptidomimetic antibiotics that target LptD in Pseudomonas sp. Bioorg.Med.Chem., 21:5806-5810, 2013 Cited by PubMed Abstract: We report structural studies in aqueous solution on backbone cyclic peptides that possess potent antimicrobial activity specifically against Pseudomonas sp. The peptides target the β-barrel outer membrane protein LptD, which plays an essential role in lipopolysaccharide transport to the outer membrane. The peptide L27-11 contains a 12-residue loop (T(1)W(2)L(3)K(4)K(5)R(6)R(7)W(8)K(9)K(10)A(11)K(12)) linked to a DPro-LPro template. Two related peptides were also studied, one with various Lys to ornithine or diaminobutyric acid substitutions as well as a DLys(6) (called LB-01), and another containing the same loop sequence, but linked to an LPro-DPro template (called LB-02). NMR studies and MD simulations show that L27-11 and LB-01 adopt β-hairpin structures in solution. In contrast, LB-02 is more flexible and importantly, adopts a wide variety of different backbone conformations, but not β-hairpin conformations. L27-11 and LB-01 show antimicrobial activity in the nanomolar range against Pseudomonas aeruginosa, whereas LB-02 is essentially inactive. Thus the β-hairpin structure of the peptide is important for antimicrobial activity. An alanine scan of L27-11 revealed that tryptophan side chains (W(2)/W(8)) displayed on opposite faces of the β-hairpin represent key groups contributing to antimicrobial activity. PubMed: 23932450DOI: 10.1016/j.bmc.2013.07.013 PDB entries with the same primary citation |
Experimental method | SOLUTION NMR |
Structure validation
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