PDBsum entry 1vbs

Isomerase/ isomerase substrate

PDB id

1vbs

Contents

			Protein chain

					164 a.a. *

			Ligands

					ALA-DAL-PRO-PHE- NIT

			Waters ×267

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Mapping the stereospecificity of peptidyl prolyl cis/trans isomerases.

Authors

C.Schiene, U.Reimer, M.Schutkowski, G.Fischer.

Ref.

Febs Lett, 1998, 432, 202-206. [DOI no: 10.1016/S0014-5793(98)00871-0]

PubMed id

9720925

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a percentage match of 0%.

Abstract

The stereospecificity of peptidyl prolyl cis/trans isomerases (PPIases) was studied using tetrapeptide substrate analogs in which one amino acid residue was replaced by the cognate D-amino acid in various positions of the peptide chain. Reversed stereocenters around proline markedly increased the rate of the spontaneous trans to cis isomerization of the prolyl bond whereas cis to trans isomerizations were less sensitive. PPIases like human cyclophilin18, human FKBP12, Escherichia coli parvulin10 and the PPIase domain of E. coli trigger factor exhibited stereoselectivity demanding at the P1 to P2' position of the substrate chain. The discriminating factor for stereoselectivity was the lack of formation of the Michaelis complexes of the diastereomeric substrates. However, D-alanine at the P1 position preserved considerable affinity to the active site, and largely prevented activation of the catalytic machinery for all PPIases investigated.



	Figure 1. Fig. 1. Time course of fluorescence at 416 nm after jumping from the peptide stock solution in TFE/LiCl into the final buffer solution using 20 μM Abz-Ala-Ala-Pro-Phe-NH-Np at 10°C. A, uncatalyzed (k=7.9×10^3 s^−1); B, 1 nM rhCyp18cy (k=15.3×10^3 s^−1). Measurements were done in 35 mM HEPES pH 7.8, λ[ex]=320 nm.

PROCHECK

	Headers