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1.
Br J Cancer ; 119(3): 347-356, 2018 08.
Article in English | MEDLINE | ID: mdl-29988112

ABSTRACT

BACKGROUND: A significant subset of prostate cancer (PC) patients with a castration-resistant form of the disease (CRPC) show primary resistance to androgen receptor (AR)-targeting drugs developed against CRPC. As one explanation could be the expression of constitutively active androgen receptor splice variants (AR-Vs), our current objectives were to study AR-Vs and other AR aberrations to better understand the emergence of CRPC. METHODS: We analysed specimens from different stages of prostate cancer by next-generation sequencing and immunohistochemistry. RESULTS: AR mutations and copy number variations were detected only in CRPC specimens. Genomic structural rearrangements of AR were observed in 5/30 metastatic CRPC patients, but they were not associated with expression of previously known AR-Vs. The predominant AR-Vs detected were AR-V3, AR-V7 and AR-V9, with the expression levels being significantly higher in CRPC cases compared to prostatectomy samples. Out of 25 CRPC metastases that expressed any AR variant, 17 cases harboured expression of all three of these AR-Vs. AR-V7 protein expression was highly heterogeneous and higher in CRPC compared to hormone-naïve tumours. CONCLUSIONS: AR-V3, AR-V7 and AR-V9 are co-expressed in CRPC metastases highlighting the fact that inhibiting AR function via regions common to all AR-Vs is likely to provide additional benefit to patients with CRPC.


Subject(s)
Prostatic Hyperplasia/genetics , Prostatic Neoplasms, Castration-Resistant/genetics , Protein Isoforms/genetics , Receptors, Androgen/genetics , Androgens/genetics , Cell Line, Tumor , DNA Copy Number Variations/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Neoplasm Metastasis , Prostate/metabolism , Prostate/pathology , Prostatic Hyperplasia/pathology , Prostatic Hyperplasia/surgery , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/surgery , RNA Splicing/genetics , Exome Sequencing , Whole Genome Sequencing
2.
Am J Surg Pathol ; 42(1): 103-115, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28984675

ABSTRACT

Advances in prostate cancer biology and diagnostics are dependent upon high-fidelity integration of clinical, histomorphologic, and molecular phenotypic findings. In this study, we compared fresh frozen, formalin-fixed paraffin-embedded (FFPE), and PAXgene-fixed paraffin-embedded (PFPE) tissue preparation methods in radical prostatectomy prostate tissue from 36 patients and performed a preliminary test of feasibility of using PFPE tissue in routine prostate surgical pathology diagnostic assessment. In addition to comparing histology, immunohistochemistry, and general measures of DNA and RNA integrity in each fixation method, we performed functional tests of DNA and RNA quality, including targeted Miseq RNA and DNA sequencing, and implemented methods to relate DNA and RNA yield and quality to quantified DNA and RNA picogram nuclear content in each tissue volume studied. Our results suggest that it is feasible to use PFPE tissue for routine robot-assisted laparoscopic prostatectomy surgical pathology diagnostics and immunohistochemistry, with the benefit of significantly improvedDNA and RNA quality and RNA picogram yield per nucleus as compared with FFPE tissue. For fresh frozen, FFPE, and PFPE tissues, respectively, the average Genomic Quality Numbers were 7.9, 3.2, and 6.2, average RNA Quality Numbers were 8.7, 2.6, and 6.3, average DNA picogram yields per nucleus were 0.41, 0.69, and 0.78, and average RNA picogram yields per nucleus were 1.40, 0.94, and 2.24. These findings suggest that where DNA and/or RNA analysis of tissue is required, and when tissue size is small, PFPE may provide important advantages over FFPE. The results also suggest several interesting nuances including potential avenues to improve RNA quality in FFPE tissues and confirm recent suggestions that some DNA sequence artifacts associated with FFPE can be avoided.


Subject(s)
Histocytological Preparation Techniques/methods , Pathology, Surgical/methods , Prostate/pathology , DNA/isolation & purification , Feasibility Studies , Fixatives , Humans , Immunohistochemistry , Male , Prostate/surgery , Prostatectomy , RNA/isolation & purification , Sequence Analysis, DNA , Sequence Analysis, RNA
3.
Gene ; 626: 119-131, 2017 Aug 30.
Article in English | MEDLINE | ID: mdl-28502869

ABSTRACT

Fast progress of the next generation sequencing (NGS) technology has allowed global transcriptional profiling and genome-wide mapping of transcription factor binding sites in various cellular contexts. However, limited number of replicates and high amount of data processing may weaken the significance of the findings. Comparative analyses of independent data sets acquired in the different laboratories would greatly increase the validity of the data. Runx2 is the key transcription factor regulating osteoblast differentiation and bone formation. We performed a comparative analysis of three published Runx2 data sets of chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) analysis in osteoblasts from mouse and human origin. Moreover, we assessed the similarity of the corresponding transcription data of these studies available online. The ChIP-seq data analysis confirmed general features of Runx2 binding, including location at genic vs intergenic regions and abundant Runx2 binding on promoters of the highly expressed genes. We also found high frequency of Runx2 DNA binding without a consensus Runx2 motif at the binding site. Importantly, mouse and human Runx2 showed moderately similar binding patterns in terms of peak-associated closest genes and their associated genomic ontology (GO) pathways. Accordingly, the gene expression profiles were highly similar and osteoblastic phenotype was prominent in the differentiated stage in both species. In conclusion, ChIP-seq method shows good reproducibility in the context of mature osteoblasts, and mouse and human osteoblast models resemble each other closely in Runx2 binding and in gene expression profiles, supporting the use of these models as adequate tools in studying osteoblast differentiation.


Subject(s)
Chromatin/metabolism , Core Binding Factor Alpha 1 Subunit/genetics , Osteoblasts/metabolism , Animals , Cell Line , Chromatin Immunoprecipitation/standards , Core Binding Factor Alpha 1 Subunit/metabolism , Humans , Mice , Nucleotide Motifs , Promoter Regions, Genetic , Protein Binding , Reproducibility of Results , Species Specificity , Transcriptional Activation
4.
Structure ; 21(12): 2107-18, 2013 Dec 03.
Article in English | MEDLINE | ID: mdl-24207127

ABSTRACT

Collagen prolyl 4-hydroxylase (C-P4H) catalyzes the proline hydroxylation of procollagen, an essential modification in the maturation of collagens. C-P4H consists of two catalytic α subunits and two protein disulfide isomerase ß subunits. The assembly of these subunits is unknown. The α subunit contains an N domain (1-143), a peptide-substrate-binding-domain (PSB, 144-244) and a catalytic domain (245-517). Here, we report the dimeric structure of the N-terminal region (1-244) of the α subunit. It is shown that the N domain has an important role in the assembly of the C-P4H tetramer, by forming an extended four-helix bundle that includes an antiparallel coiled-coil dimerization motif between the two α subunits. Complexes of this construct with a C-P4H inhibitor and substrate show the mode of peptide-binding to the PSB domain. Both peptides adopt a poly-(L)-proline-type-II helix conformation and bind in a curved, asymmetric groove lined by conserved tyrosines and an Arg-Asp salt bridge.


Subject(s)
Procollagen-Proline Dioxygenase/chemistry , Amino Acid Motifs , Amino Acid Sequence , Crystallography, X-Ray , Humans , Models, Molecular , Molecular Sequence Data , Peptides/chemistry , Protein Binding , Protein Conformation , Protein Multimerization , Protein Subunits/chemistry , Substrate Specificity
5.
J Biol Chem ; 284(37): 25290-301, 2009 Sep 11.
Article in English | MEDLINE | ID: mdl-19553701

ABSTRACT

Plant and algal prolyl 4-hydroxylases (P4Hs) are key enzymes in the synthesis of cell wall components. These monomeric enzymes belong to the 2-oxoglutarate dependent superfamily of enzymes characterized by a conserved jelly-roll framework. This algal P4H has high sequence similarity to the catalytic domain of the vertebrate, tetrameric collagen P4Hs, whereas there are distinct sequence differences with the oxygen-sensing hypoxia-inducible factor P4H subfamily of enzymes. We present here a 1.98-A crystal structure of the algal Chlamydomonas reinhardtii P4H-1 complexed with Zn(2+) and a proline-rich (Ser-Pro)(5) substrate. This ternary complex captures the competent mode of binding of the peptide substrate, being bound in a left-handed (poly)l-proline type II conformation in a tunnel shaped by two loops. These two loops are mostly disordered in the absence of the substrate. The importance of these loops for the function is confirmed by extensive mutagenesis, followed up by enzyme kinetic characterizations. These loops cover the central Ser-Pro-Ser tripeptide of the substrate such that the hydroxylation occurs in a highly buried space. This novel mode of binding does not depend on stacking interactions of the proline side chains with aromatic residues. Major conformational changes of the two peptide binding loops are predicted to be a key feature of the catalytic cycle. These conformational changes are probably triggered by the conformational switch of Tyr(140), as induced by the hydroxylation of the proline residue. The importance of these findings for understanding the specific binding and hydroxylation of (X-Pro-Gly)(n) sequences by collagen P4Hs is also discussed.


Subject(s)
Crystallography, X-Ray/methods , Eukaryota/enzymology , Procollagen-Proline Dioxygenase/chemistry , Proline/chemistry , Amino Acid Motifs , Amino Acid Sequence , Catalytic Domain , Collagen/chemistry , Escherichia coli/metabolism , Molecular Conformation , Molecular Sequence Data , Mutation , Peptides/chemistry , Protein Binding , Sequence Homology, Amino Acid
6.
J Biol Chem ; 282(51): 37112-23, 2007 Dec 21.
Article in English | MEDLINE | ID: mdl-17940281

ABSTRACT

Prolyl 4-hydroxylases (P4Hs) are 2-oxoglutarate dioxygenases that catalyze the hydroxylation of peptidyl prolines. They play an important role in collagen synthesis, oxygen homeostasis, and plant cell wall formation. We describe four structures of a P4H from the green alga Chlamydomonas reinhardtii, two of the apoenzyme at 1.93 and 2.90 A resolution, one complexed with the competitive inhibitor Zn2+, and one with Zn2+ and pyridine 2,4-dicarboxylate (which is an analogue of 2-oxoglutarate) at 1.85 A resolution. The structures reveal the double-stranded beta-helix core fold (jellyroll motif), typical for 2-oxoglutarate dioxygenases. The catalytic site is at the center of an extended shallow groove lined by two flexible loops. Mutagenesis studies together with the crystallographic data indicate that this groove participates in the binding of the proline-rich peptide-substrates. It is discussed that the algal P4H and the catalytic domain of collagen P4Hs have notable structural similarities, suggesting that these enzymes form a separate structural subgroup of P4Hs different from the hypoxia-inducible factor P4Hs. Key structural differences between these two subgroups are described. These studies provide first insight into the structure-function relationships of the collagen P4Hs, which unlike the hypoxia-inducible factor P4Hs use proline-rich peptides as their substrates.


Subject(s)
Algal Proteins/chemistry , Chlamydomonas reinhardtii/enzymology , Procollagen-Proline Dioxygenase/chemistry , Protozoan Proteins/chemistry , Algal Proteins/metabolism , Animals , Binding Sites/physiology , Cell Wall/enzymology , Crystallography, X-Ray , Enzyme Inhibitors/chemistry , Peptides/chemistry , Peptides/metabolism , Procollagen-Proline Dioxygenase/metabolism , Proline/chemistry , Proline/metabolism , Protein Structure, Secondary/physiology , Protein Structure, Tertiary/physiology , Protozoan Proteins/metabolism , Pyridines/chemistry , Structure-Activity Relationship , Substrate Specificity/physiology , Zinc/chemistry
7.
Plant Cell ; 19(1): 256-69, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17220203

ABSTRACT

Prolyl 4-hydroxylases (P4Hs) catalyze formation of 4-hydroxyproline (4Hyp), which is found in many plant glycoproteins. We cloned and characterized Cr-P4H-1, one of 10 P4H-like Chlamydomonas reinhardtii polypeptides. Recombinant Cr-P4H-1 is a soluble 29-kD monomer that effectively hydroxylated in vitro both poly(l-Pro) and synthetic peptides representing Pro-rich motifs found in the Chlamydomonas cell wall Hyp-rich glycoprotein (HRGP) GP1. Similar Pro-rich repeats that are likely to be Cr-P4H-1 substrates are also present in the cell wall HRGP GP2 and probably GP3. Suppression of the gene encoding Cr-P4H-1 by RNA interference led to a defective cell wall consisting of a loose network of fibrils resembling the inner and outer W1 and W7 layers of the wild-type wall, while the layers forming the dense central triplet were absent. The lack of Cr-P4H-1 most probably affected 4Hyp content of the major HRPGs of the central triplet, GP1, GP2, and GP3. The reduced 4Hyp levels in these HRGPs can also be expected to affect their glycosylation and, thus, the interactive properties and stabilities of their fibrous shafts. Interestingly, our RNA interference data indicate that the nine other Chlamydomonas P4H-like polypeptides could not fully compensate for the lack of Cr-P4H-1 activity and are therefore likely to have different substrate specificities and functions.


Subject(s)
Algal Proteins/genetics , Cell Wall/enzymology , Chlamydomonas reinhardtii/enzymology , Procollagen-Proline Dioxygenase/genetics , Algal Proteins/antagonists & inhibitors , Algal Proteins/chemistry , Algal Proteins/physiology , Amino Acid Sequence , Animals , Chlamydomonas reinhardtii/genetics , Cloning, Molecular , Genome, Protozoan , Hydroxyproline/metabolism , Molecular Sequence Data , Phylogeny , Procollagen-Proline Dioxygenase/antagonists & inhibitors , Procollagen-Proline Dioxygenase/chemistry , Procollagen-Proline Dioxygenase/physiology , RNA Interference , Recombinant Fusion Proteins/metabolism , Sequence Alignment , Substrate Specificity
8.
J Biol Chem ; 279(50): 52255-61, 2004 Dec 10.
Article in English | MEDLINE | ID: mdl-15456751

ABSTRACT

Collagen prolyl 4-hydroxylases catalyze the formation of 4-hydroxyproline in -X-Pro-Gly-sequences and have an essential role in collagen synthesis. The vertebrate enzymes are alpha2beta2 tetramers in which the catalytic alpha-subunits contain separate peptide-substrate-binding and catalytic domains. We report on the crystal structure of the peptide-substrate-binding domain of the human type I enzyme refined at 2.3 A resolution. It was found to belong to a family of tetratricopeptide repeat domains that are involved in many protein-protein interactions and consist of five alpha-helices forming two tetratricopeptide repeat motifs plus the solvating helix. A prominent feature of its concave surface is a deep groove lined by tyrosines, a putative binding site for proline-rich Tripeptides. Solvent-exposed side chains of three of the tyrosines have a repeat distance similar to that of a poly-L-proline type II helix. The aromatic surface ends at one of the tyrosines, where the groove curves almost 90 degrees away from the linear arrangement of the three tyrosine side chains, possibly inducing a bent conformation in the bound peptide. This finding is consistent with previous suggestions by others that a minimal structural requirement for proline 4-hydroxylation may be a sequence in the poly-L-proline type II conformation followed by a beta-turn in the Pro-Gly segment. Site-directed mutagenesis indicated that none of the tyrosines was critical for tetramer assembly, whereas most of them were critical for the binding of a peptide substrate and inhibitor both to the domain and the alpha2beta2 enzyme tetramer.


Subject(s)
Collagen/biosynthesis , Procollagen-Proline Dioxygenase/chemistry , Procollagen-Proline Dioxygenase/metabolism , Amino Acid Sequence , Catalytic Domain , Crystallography, X-Ray , Humans , Hydrophobic and Hydrophilic Interactions , In Vitro Techniques , Models, Molecular , Molecular Sequence Data , Mutagenesis, Site-Directed , Procollagen-Proline Dioxygenase/genetics , Protein Structure, Tertiary , Protein Subunits , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Repetitive Sequences, Amino Acid , Substrate Specificity
9.
J Biol Chem ; 278(48): 47685-93, 2003 Nov 28.
Article in English | MEDLINE | ID: mdl-14500733

ABSTRACT

Collagen prolyl 4-hydroxylases (C-P4Hs) catalyze the formation of 4-hydroxyproline by the hydroxylation of -X-Pro-Gly-triplets. The vertebrate enzymes are alpha 2 beta 2 tetramers, the beta-subunit being identical to protein-disulfide isomerase (PDI). Two isoforms of the catalytic alpha-subunit, which combine with PDI to form [alpha(I)]2 beta 2 and [alpha(II)]2 beta 2 tetramers, have been known up to now. We report here on the cloning and characterization of a third vertebrate C-P4H alpha-subunit isoform, alpha(III). The processed human, rat and mouse alpha(III) polypeptides consist of 520-525 residues, all three having signal peptides of 19-22 additional residues. The sequence of the processed human alpha(III) polypeptide is 35-37% identical to those of human alpha(I) and alpha(II), the highest identity being found within the catalytically important C-terminal region and all five critical residues at the cosubstrate binding sites being conserved. The sequence within a region corresponding to the peptide-substrate binding domain is less conserved, but all five alpha helices constituting this domain can be predicted to be located in identical positions in alpha(I), alpha(II), and alpha(III) and to have essentially identical lengths. The alpha(III) mRNA is expressed in many human tissues, but at much lower levels than the alpha(I) and alpha(II) mRNAs. In contrast to alpha(I) and alpha(II), no evidence was found for alternative splicing of the alpha(III) transcripts. Coexpression of a recombinant human alpha(III) polypeptide with PDI in human embryonic kidney cells led to the formation of an active enzyme that hydroxylated collagen chains and a collagen-like peptide and appeared to be an [alpha(III)]2 beta 2 tetramer. The catalytic properties of the recombinant enzyme were very similar to those of the type I and II C-P4Hs, with the exception that its peptide binding properties were intermediate between those of the type I and type II enzymes.


Subject(s)
Procollagen-Proline Dioxygenase/chemistry , Amino Acid Sequence , Animals , Binding Sites , Blotting, Northern , Catalysis , Catalytic Domain , Cell Line , Cloning, Molecular , Collagen/chemistry , Cysteine/chemistry , DNA, Complementary/metabolism , Dose-Response Relationship, Drug , Electrophoresis, Polyacrylamide Gel , Humans , Immunoblotting , Inhibitory Concentration 50 , Insecta , Kinetics , Mice , Models, Genetic , Molecular Sequence Data , Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase/chemistry , Peptides/chemistry , Precipitin Tests , Protein Isoforms , Protein Sorting Signals , Protein Structure, Tertiary , RNA, Messenger/metabolism , Rats , Recombinant Proteins/chemistry , Sequence Homology, Amino Acid , Tissue Distribution , beta-Galactosidase/metabolism
10.
Acta Crystallogr D Biol Crystallogr ; 59(Pt 5): 940-2, 2003 May.
Article in English | MEDLINE | ID: mdl-12777818

ABSTRACT

Collagen prolyl 4-hydroxylases catalyze the hydroxylation of -X-Pro-Gly- sequences and play an essential role in the synthesis of all collagens. They require Fe(2+), 2-oxoglutarate, molecular oxygen and ascorbate, and all vertebrate collagen prolyl 4-hydroxylases are alpha(2)beta(2) tetramers. The alpha-subunits contain separate catalytic and peptide substrate-binding domains. Here, the crystallization of the peptide substrate-binding domain consisting of residues 144-244 of the 517-residue human alpha(I) subunit is described. The crystals are well ordered and diffract to at least 3 A. The space group is P3(1) or P3(2) and the asymmetric unit most probably contains a dimer.


Subject(s)
Collagen Type I/metabolism , Procollagen-Proline Dioxygenase/chemistry , Proline/chemistry , Crystallization , Humans , Peptides/chemistry , Peptides/metabolism , Procollagen-Proline Dioxygenase/genetics , Procollagen-Proline Dioxygenase/metabolism , Protein Structure, Tertiary , Protein Subunits/chemistry , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , X-Ray Diffraction
11.
J Biol Chem ; 278(37): 34966-74, 2003 Sep 12.
Article in English | MEDLINE | ID: mdl-12824157

ABSTRACT

The collagen prolyl 4-hydroxylases (C-P4Hs) catalyze the formation of 4-hydroxyproline by the hydroxylation of proline residues in -Xaa-Pro-Gly-sequences. The vertebrate enzymes are alpha 2 beta 2 tetramers in which protein-disulfide isomerase serves as the beta subunit. Two isoforms of the catalytic alpha subunit have been identified and shown to form [alpha(I)]2 beta 2 and [alpha(II)]2 beta 2 tetramers, the type I and type II C-P4Hs, respectively. The peptide-substrate-binding domain of type I C-P4H has been shown to be located between residues 138 and 244 in the 517-residue alpha(I) subunit and to be distinct from the catalytic domain that is located in the C-terminal region. We report here that a recombinant human C-P4H alpha(I) polypeptide Phe144-Ser244 forms a folded domain consisting of five alpha helices and one short beta strand. This structure is quite different from those of other proline-rich peptide-binding modules, which consist mainly of beta strands. Binding of the peptide (Pro-Pro-Gly)2 to this domain caused major chemical shifts in many backbone amide resonances, the residues showing the largest shifts being mainly hydrophobic, including three tyrosines. The Kd values determined by surface plasmon resonance and isothermal titration calorimetry for the binding of several synthetic peptides to the alpha(I) and the corresponding alpha(II) domain were very similar to the Km and Ki values for these peptides as substrates and inhibitors of the type I and type II C-P4H tetramers. The Kd values of the alpha(I) and alpha(II) domains for (Gly-Pro-4Hyp)5 were much higher than those for (Pro-Pro-Gly)5, indicating a marked decrease in the affinity of hydroxylated peptides for the domain. Many characteristic features of the binding of peptides to the type I and type II C-P4H tetramers can thus be explained by the properties of binding to this domain rather than the catalytic domain.


Subject(s)
Collagen/metabolism , Peptides/metabolism , Procollagen-Proline Dioxygenase/chemistry , Procollagen-Proline Dioxygenase/metabolism , Proline , Amino Acid Sequence , Binding Sites , Circular Dichroism , Humans , Molecular Sequence Data , Peptides/chemistry , Protein Conformation , Protein Structure, Secondary , Protein Subunits/chemistry , Protein Subunits/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Substrate Specificity
12.
J Biol Chem ; 277(26): 23965-71, 2002 Jun 28.
Article in English | MEDLINE | ID: mdl-11976332

ABSTRACT

4-Hydroxyproline is found in collagens and collagen-like proteins in animals and in many glycoproteins in plants. Animal prolyl 4-hydroxylases (P4Hs) have been cloned and characterized from many sources, but no plant P4H has been cloned so far. We report here that the genome of Arabidopsis thaliana encodes six P4H-like polypeptides, one of which, a 283-residue soluble monomer, was cloned and characterized here as a recombinant protein. Catalytically critical residues identified in animal P4Hs are conserved in this P4H, and their mutagenesis led to complete or almost complete inactivation. The recombinant P4H effectively hydroxylated poly(l-proline) and many synthetic peptides corresponding to proline-rich repeats present in plant glycoproteins and other proteins. Surprisingly, collagen-like peptides were also good substrates, the V(max) with (Pro-Pro-Gly)(10) being similar to that with poly(l-proline). The enzyme acted in this peptide preferentially on prolines in Y positions in the X-Y-Gly triplets. Correspondingly, (Gly-Pro-4Hyp)(5) and (Pro-Ala-Gly)(5) were poor substrates, with V(max) values less than 5 and 20% of that obtained with (Pro-Pro-Gly)(10), respectively, the K(m) for the latter also being high. Peptides representing the N- and C-terminal hydroxylation sites present in hypoxia-inducible transcription factor alpha also served as substrates. As these peptides contain only one proline residue, a poly(l-proline) type II conformation was clearly not required for hydroxylation.


Subject(s)
Arabidopsis/enzymology , Collagen/metabolism , Procollagen-Proline Dioxygenase/genetics , Transcription Factors/metabolism , Amino Acid Sequence , Animals , Catalysis , Cloning, Molecular , Hydroxylation , Hypoxia-Inducible Factor 1, alpha Subunit , Molecular Sequence Data , Molecular Weight , Procollagen-Proline Dioxygenase/chemistry , Procollagen-Proline Dioxygenase/metabolism , Recombinant Proteins/biosynthesis , Spodoptera
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