5lo2

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Engineering protein stability with atomic precision in a monomeric miniprotein

Structural highlights

5lo2 is a 1 chain structure with sequence from Streptococcus mutans. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR, 20 models
Ligands:ACE, NH2
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SPAP_STRMU Surface protein antigen implicated in dental caries.

Publication Abstract from PubMed

Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPalpha-Tyr, a designed peptide comprising an alpha-helix buttressed by a polyproline II helix. PPalpha-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding temperature (TM) of 39 degrees C. NMR structures of PPalpha-Tyr reveal proline residues docked between tyrosine side chains, as designed. The stability of PPalpha is sensitive to modifications in the aromatic residues: replacing tyrosine with phenylalanine, i.e., changing three solvent-exposed hydroxyl groups to protons, reduces the TM to 20 degrees C. We attribute this result to the loss of CH-pi interactions between the aromatic and proline rings, which we probe by substituting the aromatic residues with nonproteinogenic side chains. In analyses of natural protein structures, we find a preference for proline-tyrosine interactions over other proline-containing pairs, and observe abundant CH-pi interactions in biologically important complexes between proline-rich ligands and SH3 and similar domains.

Engineering protein stability with atomic precision in a monomeric miniprotein.,Baker EG, Williams C, Hudson KL, Bartlett GJ, Heal JW, Porter Goff KL, Sessions RB, Crump MP, Woolfson DN Nat Chem Biol. 2017 Jul;13(7):764-770. doi: 10.1038/nchembio.2380. Epub 2017 May , 22. PMID:28530710[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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References

  1. Baker EG, Williams C, Hudson KL, Bartlett GJ, Heal JW, Porter Goff KL, Sessions RB, Crump MP, Woolfson DN. Engineering protein stability with atomic precision in a monomeric miniprotein. Nat Chem Biol. 2017 Jul;13(7):764-770. doi: 10.1038/nchembio.2380. Epub 2017 May , 22. PMID:28530710 doi:http://dx.doi.org/10.1038/nchembio.2380

Contents


PDB ID 5lo2

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