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PDBsum entry 1vai

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Isomerase PDB id
1vai
Jmol
Contents
Protein chains
166 a.a. *
Ligands
ACE-ALA-ALA-PRO-
ALA-MCM
Waters ×197
* Residue conservation analysis

References listed in PDB file
Key reference
Title Escherichia coli cyclophilin b binds a highly distorted form of trans-Prolyl peptide isomer.
Authors M.Konno, Y.Sano, K.Okudaira, Y.Kawaguchi, Y.Yamagishi-Ohmori, S.Fushinobu, H.Matsuzawa.
Ref. Eur J Biochem, 2004, 271, 3794-3803. [DOI no: 10.1111/j.1432-1033.2004.04321.x]
PubMed id 15355356
Abstract
Cyclophilins facilitate the peptidyl-prolyl isomerization of a trans-isomer to a cis-isomer in the refolding process of unfolded proteins to recover the natural folding state with cis-proline conformation. To date, only short peptides with a cis-form proline have been observed in complexes of human and Escherichia coli proteins of cyclophilin A, which is present in cytoplasm. The crystal structures analyzed in this study show two complexes in which peptides having a trans-form proline, i.e. succinyl-Ala-trans-Pro-Ala-p-nitroanilide and acetyl-Ala-Ala-trans-Pro-Ala-amidomethylcoumarin, are bound on a K163T mutant of Escherichia coli cyclophilin B, the preprotein of which has a signal sequence. Comparison with cis-form peptides bound to cyclophilin A reveals that in any case the proline ring is inserted into the hydrophobic pocket and a hydrogen bond between CO of Pro and Neta2 of Arg is formed to fix the peptide. On the other hand, in the cis-isomer, the formation of two hydrogen bonds of NH and CO of Ala preceding Pro with the protein fixes the peptide, whereas in the trans-isomer formation of a hydrogen bond between CO preceding Ala-Pro and His47 Nepsilon2 via a mediating water molecule allows the large distortion in the orientation of Ala of Ala-Pro. Although loss of double bond character of the amide bond of Ala-Pro is essential to the isomerization pathway occurring by rotating around its bond, these peptides have forms impossible to undergo proton transfer from the guanidyl group of Arg to the prolyl N atom, which induces loss of double bond character.
Figure 2.
Fig. 2. The ribbon model of the -barrel structure of E. coli CyPB consisting of the upper and the lower -sheets enclosed by two helices. The colors of ribbon are shown corresponding to those of Fig. 1. The loop colored in green is the region expected to affect the selection of the substrate. Thr163 is located outside of 8 strand. The Suc-Ala-trans-Pro-Ala-pNA is also shown by ball-and-sticks model. Figures 2,3,4,5,6 and 7 were prepared using the programs MOLSCRIPT[35] and RASTER3D[36].
Figure 4.
Fig. 4. A stereo view of Suc-Ala-trans-Pro-Ala-pNA (green) and Ac-Ala-Ala-trans-Pro-Ala-AMC (yellow) bound to superimposed E. coli CyPB molecules. The hydrogen bonds are shown in broken lines. The CyPB molecules shown in Figs 4, 6 and 7 were rotated by 45° around the horizontal axis from those shown in Figs 2 and 3.
The above figures are reprinted by permission from the Federation of European Biochemical Societies: Eur J Biochem (2004, 271, 3794-3803) copyright 2004.
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