4QFP

Crystal structure of dipeptide binding protein from pseudoalteromonas sp. SM9913 in complex with Val-Thr

Summary for 4QFP

• Entry DOI: 10.2210/pdb4qfp/pdb
• Related: 4QFK 4QFL 4QFN 4QFO
• Descriptor: ABC transporter periplasmic peptide-binding protein, VALINE, THREONINE, ... (6 entities in total)
• Functional Keywords: dipeptide binding protein, peptide binding protein
• Biological source: Pseudoalteromonas
• Total number of polymer chains: 2
• Total formula weight: 124372.53

Authors

Li, C.Y.,Zhang, Y.Z. (deposition date: 2014-05-21, release date: 2015-01-28, Last modification date: 2024-10-30)

Primary citation

Li, C.Y.,Chen, X.L.,Qin, Q.L.,Wang, P.,Zhang, W.X.,Xie, B.B.,Su, H.N.,Zhang, X.Y.,Zhou, B.C.,Zhang, Y.Z.
Structural insights into the multispecific recognition of dipeptides of deep-sea gram-negative bacterium Pseudoalteromonas sp. strain SM9913
J. Bacteriol., 197:1125-1134, 2015

PubMed Abstract: Peptide uptake is important for nutrition supply for marine bacteria. It is also an important step in marine nitrogen cycling. However, how marine bacteria absorb peptides is still not fully understood. DppA is the periplasmic dipeptide binding protein of dipeptide permease (Dpp; an important peptide transporter in bacteria) and exclusively controls the substrate specificity of Dpp. Here, the substrate binding specificity of deep-sea Pseudoalteromonas sp. strain SM9913 DppA (PsDppA) was analyzed for 25 different dipeptides with various properties by using isothermal titration calorimetry measurements. PsDppA showed binding affinities for 8 dipeptides. To explain the multispecific substrate recognition mechanism of PsDppA, we solved the crystal structures of unliganded PsDppA and of PsDppA in complex with 4 different types of dipeptides (Ala-Phe, Met-Leu, Gly-Glu, and Val-Thr). PsDppA alternates between an "open" and a "closed" form during substrate binding. Structural analyses of the 4 PsDppA-substrate complexes combined with mutational assays indicate that PsDppA binds to different substrates through a precise mechanism: dipeptides are bound mainly by the interactions between their backbones and PsDppA, in particular by anchoring their N and C termini through ion-pair interactions; hydrophobic interactions are important in binding hydrophobic dipeptides; and Lys457 is necessary for the binding of dipeptides with a C-terminal glutamic acid or glutamine. Additionally, sequence alignment suggests that the substrate recognition mechanism of PsDppA may be common in Gram-negative bacteria. All together, our results provide structural insights into the multispecific substrate recognition mechanism of marine Gram-negative bacterial DppA, which provides a better understanding of the mechanisms of marine bacterial peptide uptake.

PubMed: 25605306
DOI: 10.1128/JB.02600-14

Experimental method

X-RAY DIFFRACTION (1.903 Å)