# COLLAGEN FOLDING IN PRESENCE OF CIS-TRANS ISOMERASE

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 1990 · $68,387

## Abstract

Folding is an essential step of biosynthesis of proteins because
biological function can only be obtained by specific structures.
This proposal focuses on the question how a recently discovered
enzyme activity termed peptidyl-prolyl cis-transisomerase
influences the triple helix formation of collagens in vitro and in
vivo.  The activity is to be purified to homogeneity from pig
kidneys and characterized in regard to molecular weight,
hydrodynamic parameters, aminoacid composition, aminoterminal
aminoacid sequence, spectroscopic properties and enzyme
kinetics.  Enzymatic activity is determined against the cis to
trans isomerization of succinyl-Ala-Ala-Pro-Phe-4-
methlycumaryl-7-amide by means of a two-step process using
chymotrypsin as the trans substrate cleaving activity.  This
enzyme probably helps folding of protein which has been shown to
be rate limited by isomerization of proline containing peptide
bonds.  To test this hypothesis the influence of peptidyl-prolyl cis-
trans isomerase on in vitro folding of type III collagen is
investigated.  Refolding of type III collagen was shown to be rate
limited by cis to trans isomerization of peptide bonds.  The
influence of ionic strength and pH on the kinetics of peptidyl-
prolyl cis-trans isomerase is investigated as well as the
intercellular localization by immunoelectronmicroscopy.  To see
whether  the enzyme is actively involved in in vivo folding during
biosynthesis, the enzyme level is investigated for correlation with
4-prolyl hydroxylase in a developing system with varying degrees
of collagen synthesis.  What happens if folding is impaired has
been shown recently in cases of Osteogenesis Imperfecta where a
single aminoacid substitution for a glycine residue in the pro alpha
1 chain of type I procollagen leads to procollagen molecules with
decreased melting temperature, increased posttranslational,
modification altered rate of secretion, increased intracellular
degradation, and decreased collagen production.

## Key facts

- **NIH application ID:** 3158047
- **Project number:** 5R01AR037322-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **SAM.gov UEI:** NPSNT86JKN51
- **Principal Investigator:** HANS PETER BACHINGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $68,387
- **Award type:** 5
- **Project period:** 1988-08-01 → 1992-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158047

## Citation

> US National Institutes of Health, RePORTER application 3158047, COLLAGEN FOLDING IN PRESENCE OF CIS-TRANS ISOMERASE (5R01AR037322-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158047. Licensed CC0.

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