5VTI

Structure of Pin1 WW Domain Sequence 3 with [R,R]-ACPC Loop Substitution

Summary for 5VTI

• Entry DOI: 10.2210/pdb5vti/pdb
• Related: 5VTJ 5VTK
• Descriptor: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, CHLORIDE ION (3 entities in total)
• Functional Keywords: beta amino acid, ww domain, phosphopeptide binding, protein binding
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q13526
• Total number of polymer chains: 1
• Total formula weight: 3845.76

Authors

Mortenson, D.E.,Kreitler, D.F.,Thomas, N.C.,Gellman, S.H.,Forest, K.T. (deposition date: 2017-05-17, release date: 2018-02-21, Last modification date: 2023-11-15)

Primary citation

Mortenson, D.E.,Kreitler, D.F.,Thomas, N.C.,Guzei, I.A.,Gellman, S.H.,Forest, K.T.
Evaluation of beta-Amino Acid Replacements in Protein Loops: Effects on Conformational Stability and Structure.
Chembiochem, 19:604-612, 2018

PubMed Abstract: β-Amino acids have a backbone that is expanded by one carbon atom relative to α-amino acids, and β residues have been investigated as subunits in protein-like molecules that adopt discrete and predictable conformations. Two classes of β residue have been widely explored in the context of generating α-helix-like conformations: β -amino acids, which are homologous to α-amino acids and bear a side chain on the backbone carbon adjacent to nitrogen, and residues constrained by a five-membered ring, such the one derived from trans-2-aminocyclopentanecarboxylic acid (ACPC). Substitution of α residues with their β  homologues within an α-helix-forming sequence generally causes a decrease in conformational stability. Use of a ring-constrained β residue, however, can offset the destabilizing effect of α→β substitution. Here we extend the study of α→β substitutions, involving both β and ACPC residues, to short loops within a small tertiary motif. We start from previously reported variants of the Pin1 WW domain that contain a two-, three-, or four-residue β-hairpin loop, and we evaluate α→β replacements at each loop position for each variant. By referral to the ϕ,ψ angles of the native structure, one can choose a stereochemically appropriate ACPC residue. Use of such logically chosen ACPC residues enhances conformational stability in several cases. Crystal structures of three β-containing Pin1 WW domain variants show that a native-like tertiary structure is maintained in each case.

PubMed: 29272560
DOI: 10.1002/cbic.201700580

Experimental method

X-RAY DIFFRACTION (1.8 Å)