Prolyl 4-hydroxylases and their protein disulfide isomerase subunit

doi:10.1016/S0945-053X(98)90009-9

Matrix Biology

Volume 16, Issue 7, February 1998, Pages 357-368

https://doi.org/10.1016/S0945-053X(98)90009-9 Get rights and content

Abstract

Prolyl 4-hydroxylases (EC 1.14.11.2) catalyze the formation of 4-hydroxyproline in collagens and other proteins with collagen-like sequences. The vertebrate type I and type II enzymes are [α(I)]₂β₂ and [α(II)]₂β₂ tetramers, respectively, whereas the enzyme from the nematode Caenorhabditis elegans is an αβ dimer. The type I enzyme is the major form in most but not all vertebrate tissues. The catalytic properties of the various enzyme forms are highly similar, but there are distinct, although small, differences in K_m values for various peptide substrates between the enzyme forms and major differences in K_i values for the competitive inhibitor, poly(L-proline). Prolyl 4-hydroxylase requires Fe²⁺, 2-oxoglutarate, O₂ and ascorbate. Kinetic studies and theoretical considerations have led to elucidation of the reaction mechanism, and recent extensive site-directed mutagenesis studies have identified five critical residues at the cosubstrate binding sites. A number of compounds have been characterized that inhibit it competitively with respect to some of the cosubstrates, and three groups of suicide inactivators have also been identified. The β subunit in all forms of prolyl 4-hydroxylase is identical to protein disulfide isomerase (PDI), a multifunctional polypeptide that also serves as a subunit in the microsomal triglyceride transfer protein, as a chaperone-like polypeptide that probably assists folding of a number of newly synthesized proteins, and in several other functions. The main role of the PDI polypeptide as a protein subunit is probably related to its chaperone function. Recent expression studies of recombinant human prolyl 4-hydroxylase subunits in a yeast have indicated that the formation of a stable enzyme tetramer in vivo requires coexpression of collagen polypeptide chains.

References (75)

P. Annunen et al.
Cloning of the human prolyl 4-hydroxylase α-subunit isoform α(II) and characterization of the type II enzyme tetramer. The α(I) and α(II) subunits do not form a mixed α(I)α(II)β₂ tetramer
J. Biol. Chem.
(1997)
P.L. Atreya et al.
Interaction of prolyl 4-hydroxylase with synthetic peptide substrates. A conformational model for collagen proline hydroxylation
J. Biol. Chem.
(1991)
M. Bickel et al.
Beneficial effects of inhibitors of prolyl 4-hydroxylase in CCl₄-induced fibrosis of the liver in rats
J. Hepatol.
(1991)
K. Böker et al.
Fibrosis of the liver in rats induced by bile duct ligation. Effects of inhibition of prolyl 4-hydroxylase
J. Hepatol
(1991)
H. Cai et al.
Chaperone-like activity of protein disulfide isomerase in the refolding of a protein with no disulfide bonds
J. Biol. Chem.
(1994)
R.I. Dowell et al.
Novel inhibitors of prolyl 4-hydroxylase. Part 4. Pyridine-2-carboxylic acid analogues with alternative 2-substituents
Eur. J. Med. Chem.
(1993)
R.B. Freedman et al.
Protein disulphide isomerase: building bridges in protein folding
Trends Biochem. Sci.
(1994)
V. Günzler et al.
Syncatalytic inactivation of prolyl 4-hydroxylase by synthetic peptides containing the unphysiologic amino acid 5-oxaproline
J. Biol. Chem.
(1988)
R. Guthapfel et al.
ATP binding and hydrolysis by the multifunctional protein disulfide isomerase
J. Biol. Chem.
(1996)
H.M. Hanauske-Abel
Prolyl 4-hydroxylase, a target enzyme for drug development. Design of suppressive agents and the in vitro effects of inhibitors and proinhibitors
J. Hepatol.
(1991)

H.M. Hanauske-Abel et al.

A stereochemical concept for the catalytic mechanism of prolylhydroxylase. Applicability to classification and design of inhibitors

J. Theor. Biol.

(1982)

T. Hayano et al.

Protein disulfide isomerase mutant lacking its isomerase activity accelerates protein folding in the cell

FEBS Lett.

(1995)

T. Helaakoski et al.

Structure and expression of the human gene for the α subunit of prolyl 4-hydroxylase. The two alternatively spliced types of mRNA correspond to two homologous exons the sequences of which are expressed in a variety of tissues

J. Biol. Chem.

(1994)

I. Hopkinson et al.

The complete cDNA derived sequence of the rat prolyl 4-hydroxylase α subunit

Gene

(1994)

J. Kemmink et al.

The folding catalyst protein disulfide isomerase is constructed of active and inactive thioredoxin modules

Curr. Biol.

(1997)

J. Koivu et al.

A single polypeptide acts both as the β subunit of prolyl 4-hydroxylase and as a protein disulfide-isomerase

J. Biol. Chem.

(1987)

M. LaMantia et al.

The essential function of yeast protein disulfide isomerase does not reside in its isomerase activity

Cell

(1993)

A. Lamberg et al.

Characterization of human type III collagen expressed in a baculovirus system. Production of a protein with a stable triple helix requires coexpression with the two types of recombinant prolyl 4-hydroxylase subunit

J. Biol. Chem.

(1996)

A. Lamberg et al.

Site-directed mutagenesis of the α subunit of human prolyl 4-hydroxylase. Identification of three histidine residues critical for catalytic activity

J. Biol. Chem.

(1995)

D. Lebeche et al.

Calcium binding properties of rabbit liver protein disulfide isomerase

Biochem. Biophys. Res. Commun.

(1994)

K. Majamaa et al.

Partial identity of the 2-oxoglutarate and ascorbate binding sites of prolyl 4-hydroxylase

J. Biol. Chem.

(1986)

J. Myllyharju et al.

Expression of wild-type and modified proα chains of human type I procollagen in insect cells leads to the formation of stable [α1(I)]₂α2(I) heterotrimers and [α1(I)]₃ homotrimers but not [α2(I)]₃ homotrimers

J. Biol. Chem.

(1997)

R. Myllylä et al.

Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase

J. Biol. Chem.

(1984)

R. Noiva et al.

Peptide binding to protein disulfide isomerase occurs at a site distinct from the active site

J. Biol. Chem.

(1993)

M. Otsu et al.

Protein disulfide isomerase associates with misfolded human lysozyme in vivo

J. Biol. Chem.

(1994)

H.R.B. Pelham

The retention signal for soluble proteins of the endoplasmic reticulum

Trends Biochem. Sci.

(1990)

A. Pirskanen et al.

Site-directed mutagenesis of human lysyl hydroxylase expressed in insect cells. Identification of histidine residues and an aspartic acid residue critical for catalytic activity

J. Biol. Chem.

(1996)

A. Puig et al.

The role of the thiol/disulfide centers and peptide binding site in the chaperone and anti-chaperone activities of protein disulfide isomerase

J. Biol. Chem.

(1994)

E. Quéméneur et al.

A major phosphoprotein of the endoplasmic reticulum is protein disulfide isomerase

J. Biol. Chem.

(1994)

K. Rupp et al.

Effects of CaBP2, the rat analog of ERp72, and of CaBP1 on the refolding of denatured reduced proteins. Comparison with protein disulphide isomerase

J. Biol. Chem.

(1994)

J. Veijola et al.

Cloning, baculovirus expression, and characterization of the α subunit of prolyl 4-hydroxylase from the nematode Caenorhabditis elegans. This α subunit forms an active αβ dimer with the human protein disulfide isomerase/β subunit

J. Biol. Chem.

(1994)

W.W. Wells et al.

Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity

J. Biol. Chem.

(1990)

K. Vuori et al.

Expression and site-directed mutagenesis of human protein disulfide-isomerase in Escherichia coli. This multifunctional polypeptide has two independently acting catalytic sites for the isomerase activity

J. Biol. Chem.

(1992)

E. Baader et al.

Inhibition of prolyl 4-hydroxylase by oxalyl acid derivatives in vitro, in isolated microsomes and in embryonic chicken tissues

Biochem. J.

(1994)

J.A. Bassuk et al.

Prolyl 4-hydroxylase: Molecular cloning and the primary structure of the α-subunit from chicken enzyme

S.-Y. Cheng et al.

The nucleotide sequence of a human cellular thyroid hormone binding protein present in endoplasmic reticulum

J. Biol. Chem.

(1987)

C.J. Cunliffe et al.

Inhibition of prolyl 4-hydroxylase by hydroxyanthraquinones

Biochem. J.

(1986)

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MinireviewProlyl 4-hydroxylases and their protein disulfide isomerase subunit

Abstract

J. Biol. Chem.

J. Biol. Chem.

J. Hepatol.

J. Hepatol

J. Biol. Chem.

Eur. J. Med. Chem.

Trends Biochem. Sci.

J. Biol. Chem.

J. Biol. Chem.

J. Hepatol.

J. Theor. Biol.

FEBS Lett.

J. Biol. Chem.

Gene

Curr. Biol.

J. Biol. Chem.

Cell

J. Biol. Chem.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Trends Biochem. Sci.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Inhibition of prolyl 4-hydroxylase by oxalyl acid derivatives in vitro, in isolated microsomes and in embryonic chicken tissues

Biochem. J.

Prolyl 4-hydroxylase: Molecular cloning and the primary structure of the α-subunit from chicken enzyme

The nucleotide sequence of a human cellular thyroid hormone binding protein present in endoplasmic reticulum

J. Biol. Chem.

Inhibition of prolyl 4-hydroxylase by hydroxyanthraquinones

Biochem. J.

Minireview
Prolyl 4-hydroxylases and their protein disulfide isomerase subunit