3-Hydroxyproline, a New Amino Acid of Collagen

Ogle, James D.; Arlinghaus, Ralph B.; Logan, Milan A.

doi:10.1016/s0021-9258(19)84504-0

Cited by 78 publications

(11 citation statements)

References 25 publications

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“…Some Lys residues in the Y-position are also hydroxylated to hydroxylysine (Hyl); these are often glycosylated and/or form covalent cross-links through an oxidation process catalyzed by lysyl oxidase during tissue maturation [ 20 – 23 ]. Until recently, only one Pro residue in the X-position, Pro 986 of the α1 chain of type I and type II collagen (the α1(I) chain and the α1(II) chain, respectively) was known to be a 3R-hydroxyproline (3Hyp), in which the hydroxyl group is appended on the β -carbon (the 3-position) of the pyrrole ring of Pro instead of the γ -carbon (the 4-position) as is the case of 4Hyp [ 24 ]. More recent studies using MS and MS/MS found that several other Pro in the X-position of fibrillar collagens were also hydroxylated [ 8 , 9 ]; some of the X-Hyps were later confirmed to be a 3Hyp by Edman sequencing.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity in proline hydroxylation of fibrillar collagens observed by mass spectrometry

Kirchner

Deng

2021

PLoS ONE

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Collagen is the major protein in the extracellular matrix and plays vital roles in tissue development and function. Collagen is also one of the most processed proteins in its biosynthesis. The most prominent post-translational modification (PTM) of collagen is the hydroxylation of Pro residues in the Y-position of the characteristic (Gly-Xaa-Yaa) repeating amino acid sequence of a collagen triple helix. Recent studies using mass spectrometry (MS) and tandem MS sequencing (MS/MS) have revealed unexpected hydroxylation of Pro residues in the X-positions (X-Hyp). The newly identified X-Hyp residues appear to be highly heterogeneous in location and percent occupancy. In order to understand the dynamic nature of the new X-Hyps and their potential impact on applications of MS and MS/MS for collagen research, we sampled four different collagen samples using standard MS and MS/MS techniques. We found considerable variations in the degree of PTMs of the same collagen from different organisms and/or tissues. The rat tail tendon type I collagen is particularly variable in terms of both over-hydroxylation of Pro in the X-position and under-hydroxylation of Pro in the Y-position. In contrast, only a few unexpected PTMs in collagens type I and type III from human placenta were observed. Some observations are not reproducible between different sequencing efforts of the same sample, presumably due to a low population and/or the unpredictable nature of the ionization process. Additionally, despite the heterogeneous preparation and sourcing, collagen samples from commercial sources do not show elevated variations in PTMs compared to samples prepared from a single tissue and/or organism. These findings will contribute to the growing body of information regarding the PTMs of collagen by MS technology, and culminate to a more comprehensive understanding of the extent and the functional roles of the PTMs of collagen.

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Section: Introductionmentioning

confidence: 99%

Heterogeneity in proline hydroxylation of fibrillar collagens observed by mass spectrometry

Kirchner

Deng

2021

PLoS ONE

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“…Despite the distinct functions of 3-HyP and 4-HyP isomers in the cell, limited approaches have been developed to identify and discriminate these two isomeric residues. Amino acid analysis was originally employed for the discovery of 3-HyP . Later, Edman degradation established itself as the standard method for analysis .…”

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confidence: 99%

“…Amino acid analysis was originally employed for the discovery of 3-HyP. 23 Later, Edman degradation established itself as the standard method for analysis. 24 With the development of modern mass spectrometry, PTM analyses have become faster and simpler.…”

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confidence: 99%

Large-Scale Differentiation and Site Specific Discrimination of Hydroxyproline Isomers by Electron Transfer/Higher-Energy Collision Dissociation (EThcD) Mass Spectrometry

Sun

Tremmel

et al. 2018

Anal. Chem.

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3- and 4-Hydroxyprolines (HyP) are regioisomers that play different roles in various species and organs. Despite their distinct functions inside cells, they are generally considered indistinguishable using mass spectrometry due to their identical masses. Here, we demonstrate, for the first time, that characteristic w ions can be produced by electron-transfer/higher energy collision dissociation (EThcD) dual fragmentation technique to confidently discriminate 3-HyP/4-HyP isomers. An integrated and high throughput strategy was developed which combined online LC separation with EThcD for large-scale differentiation of 3-HyP/4-HyP in complex samples. An automated algorithm was developed for charge state dependent characterization of 3-HyP/4-HyP isomers. Using this combined discrimination approach, we identified 108 3-HyP sites and 530 4-HyP sites from decellularized pancreas, allowing more than 5-fold increase of both 3-HyP and 4-HyP identifications compared to previous reports. This approach outperformed ETD and HCD in the analysis of HyP-containing peptides with unique capacity to generate w ions for HyP discrimination, improved fragmentation of precursor ions, as well as unambiguous localization of modifications. A high content of 3-HyP was observed in the C-terminal (GPP) domain of human CO1A1, which was previously only identified in vertebrate fibrillar collagens from tendon. Unexpectedly, some unusual HyP sites at Xaa position in Gly-HyP-Ala, Gly-HyP-Val, Gly-HyP-Gln, Gly-HyP-Ser, and Gly-HyP-Arg were also confirmed to be 3-hydroxylated, whose functions and enzymes are yet to be discovered. Overall, this novel discrimination strategy can be readily implemented into de novo sequencing or other proteomic search engines.

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“…(2 R ,3 S )-3-Hydroxyproline 5 and its epimer (2 S ,3 S )-3-hydroxyproline 6 ( cis - and trans -3-hydroxyproline, respectively) have been isolated from a wide variety of natural sources, including a dried Mediterranean sponge, hydrolysates of the antibiotic telomycin, and collagen of varied origins , and have also been identified as constituents of other natural products. , Accordingly, these amino acids have inspired significant interest from synthetic chemists, with several enantiospecific and asymmetric syntheses being reported to date, in addition to enzymatic methods for their preparation …”

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confidence: 99%

Asymmetric Syntheses of (2R,3S)-3-Hydroxyproline and (2S,3S)-3-Hydroxyproline

et al. 2018

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Two synthetic routes have been developed for the asymmetric syntheses of (2 R,3 S)- and (2 S,3 S)-3-hydroxyproline. The key synthetic step in each of these strategies is the conversion of protected α,δ-dihydroxy-β-amino esters (either 2,3- anti- or 2,3- syn-configured) into β,δ-dihydroxy-α-amino esters (protected forms thereof), via the intermediacy of the corresponding aziridinium ions. The products of these stereospecific rearrangements were then cyclized and deprotected to afford (2 R,3 S)-3-hydroxyproline and (2 S,3 S)-3-hydroxyproline as single diastereoisomers (>99:1 dr) in >26% overall yield.

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3-Hydroxyproline, a New Amino Acid of Collagen

Cited by 78 publications

References 25 publications

Heterogeneity in proline hydroxylation of fibrillar collagens observed by mass spectrometry

Heterogeneity in proline hydroxylation of fibrillar collagens observed by mass spectrometry

Large-Scale Differentiation and Site Specific Discrimination of Hydroxyproline Isomers by Electron Transfer/Higher-Energy Collision Dissociation (EThcD) Mass Spectrometry

Asymmetric Syntheses of (2R,3S)-3-Hydroxyproline and (2S,3S)-3-Hydroxyproline

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