Is protein methylation in the human lens a result of non-enzymatic methylation by S-adenosylmethionine?

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Is protein methylation in the human lens a result of non-enzymatic methylation by S-adenosylmethionine? / Truscott, Roger J W; Mizdrak, Jasminka; Friedrich, Michael G; Hooi, Michelle Y; Lyons, Brian; Jamie, Joanne F; Davies, Michael Jonathan; Wilmarth, Phillip A; David, Larry L.

In: Experimental Eye Research, Vol. 99, 06.2012, p. 48-54.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Truscott, RJW, Mizdrak, J, Friedrich, MG, Hooi, MY, Lyons, B, Jamie, JF, Davies, MJ, Wilmarth, PA & David, LL 2012, 'Is protein methylation in the human lens a result of non-enzymatic methylation by S-adenosylmethionine?', Experimental Eye Research, vol. 99, pp. 48-54. https://doi.org/10.1016/j.exer.2012.04.002

APA

Truscott, R. J. W., Mizdrak, J., Friedrich, M. G., Hooi, M. Y., Lyons, B., Jamie, J. F., ... David, L. L. (2012). Is protein methylation in the human lens a result of non-enzymatic methylation by S-adenosylmethionine? Experimental Eye Research, 99, 48-54. https://doi.org/10.1016/j.exer.2012.04.002

Vancouver

Truscott RJW, Mizdrak J, Friedrich MG, Hooi MY, Lyons B, Jamie JF et al. Is protein methylation in the human lens a result of non-enzymatic methylation by S-adenosylmethionine? Experimental Eye Research. 2012 Jun;99:48-54. https://doi.org/10.1016/j.exer.2012.04.002

Author

Truscott, Roger J W ; Mizdrak, Jasminka ; Friedrich, Michael G ; Hooi, Michelle Y ; Lyons, Brian ; Jamie, Joanne F ; Davies, Michael Jonathan ; Wilmarth, Phillip A ; David, Larry L. / Is protein methylation in the human lens a result of non-enzymatic methylation by S-adenosylmethionine?. In: Experimental Eye Research. 2012 ; Vol. 99. pp. 48-54.

Bibtex

@article{72d98560b4464365a92161dc9a7100f2,
title = "Is protein methylation in the human lens a result of non-enzymatic methylation by S-adenosylmethionine?",
abstract = "Since crystallins in the human lens do not turnover, they are susceptible to modification by reactive molecules over time. Methylation is a major post-translational lens modification, however the source of the methyl group is not known and the extent of modification across all crystallins has yet to be determined. Sites of methylation in human lens proteins were determined using HPLC/mass spectrometry following digestion with trypsin. The overall extent of protein methylation increased with age, and there was little difference in the extent of modification between soluble and insoluble crystallins. Several different cysteine and histidine residues in crystallins from adult lenses were found to be methylated with one cysteine (Cys 110 in γD crystallin) at a level approaching 70{\%}, however, methylation of crystallins was not detected in fetal or newborn lenses. S-adenosylmethionine (SAM) was quantified at significant (10-50 μM) levels in lenses, and in model experiments SAM reacted readily with N-α-tBoc-cysteine and N-α-tBoc-histidine, as well as βA3-crystallin. The pattern of lens protein methylation seen in the human lens was consistent with non-enzymatic alkylation. The in vitro data shows that SAM can act directly to methylate lens proteins and SAM was present in significant concentrations in human lens. Thus, non-enzymatic methylation of crystallins by SAM offers a possible explanation for this major human lens modification.",
keywords = "Adolescent, Adult, Aged, Aging, Chromatography, High Pressure Liquid, Cysteine, Histidine, Humans, Lens, Crystalline, Mass Spectrometry, Methylation, Middle Aged, Protein Methyltransferases, Protein Processing, Post-Translational, Proteomics, S-Adenosylmethionine, Tissue Donors, Young Adult, beta-Crystallin A Chain",
author = "Truscott, {Roger J W} and Jasminka Mizdrak and Friedrich, {Michael G} and Hooi, {Michelle Y} and Brian Lyons and Jamie, {Joanne F} and Davies, {Michael Jonathan} and Wilmarth, {Phillip A} and David, {Larry L}",
note = "Copyright {\circledC} 2012 Elsevier Ltd. All rights reserved.",
year = "2012",
month = "6",
doi = "10.1016/j.exer.2012.04.002",
language = "English",
volume = "99",
pages = "48--54",
journal = "Experimental Eye Research",
issn = "0014-4835",
publisher = "Academic Press",

}

RIS

TY - JOUR

T1 - Is protein methylation in the human lens a result of non-enzymatic methylation by S-adenosylmethionine?

AU - Truscott, Roger J W

AU - Mizdrak, Jasminka

AU - Friedrich, Michael G

AU - Hooi, Michelle Y

AU - Lyons, Brian

AU - Jamie, Joanne F

AU - Davies, Michael Jonathan

AU - Wilmarth, Phillip A

AU - David, Larry L

N1 - Copyright © 2012 Elsevier Ltd. All rights reserved.

PY - 2012/6

Y1 - 2012/6

N2 - Since crystallins in the human lens do not turnover, they are susceptible to modification by reactive molecules over time. Methylation is a major post-translational lens modification, however the source of the methyl group is not known and the extent of modification across all crystallins has yet to be determined. Sites of methylation in human lens proteins were determined using HPLC/mass spectrometry following digestion with trypsin. The overall extent of protein methylation increased with age, and there was little difference in the extent of modification between soluble and insoluble crystallins. Several different cysteine and histidine residues in crystallins from adult lenses were found to be methylated with one cysteine (Cys 110 in γD crystallin) at a level approaching 70%, however, methylation of crystallins was not detected in fetal or newborn lenses. S-adenosylmethionine (SAM) was quantified at significant (10-50 μM) levels in lenses, and in model experiments SAM reacted readily with N-α-tBoc-cysteine and N-α-tBoc-histidine, as well as βA3-crystallin. The pattern of lens protein methylation seen in the human lens was consistent with non-enzymatic alkylation. The in vitro data shows that SAM can act directly to methylate lens proteins and SAM was present in significant concentrations in human lens. Thus, non-enzymatic methylation of crystallins by SAM offers a possible explanation for this major human lens modification.

AB - Since crystallins in the human lens do not turnover, they are susceptible to modification by reactive molecules over time. Methylation is a major post-translational lens modification, however the source of the methyl group is not known and the extent of modification across all crystallins has yet to be determined. Sites of methylation in human lens proteins were determined using HPLC/mass spectrometry following digestion with trypsin. The overall extent of protein methylation increased with age, and there was little difference in the extent of modification between soluble and insoluble crystallins. Several different cysteine and histidine residues in crystallins from adult lenses were found to be methylated with one cysteine (Cys 110 in γD crystallin) at a level approaching 70%, however, methylation of crystallins was not detected in fetal or newborn lenses. S-adenosylmethionine (SAM) was quantified at significant (10-50 μM) levels in lenses, and in model experiments SAM reacted readily with N-α-tBoc-cysteine and N-α-tBoc-histidine, as well as βA3-crystallin. The pattern of lens protein methylation seen in the human lens was consistent with non-enzymatic alkylation. The in vitro data shows that SAM can act directly to methylate lens proteins and SAM was present in significant concentrations in human lens. Thus, non-enzymatic methylation of crystallins by SAM offers a possible explanation for this major human lens modification.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aging

KW - Chromatography, High Pressure Liquid

KW - Cysteine

KW - Histidine

KW - Humans

KW - Lens, Crystalline

KW - Mass Spectrometry

KW - Methylation

KW - Middle Aged

KW - Protein Methyltransferases

KW - Protein Processing, Post-Translational

KW - Proteomics

KW - S-Adenosylmethionine

KW - Tissue Donors

KW - Young Adult

KW - beta-Crystallin A Chain

U2 - 10.1016/j.exer.2012.04.002

DO - 10.1016/j.exer.2012.04.002

M3 - Journal article

C2 - 22542751

VL - 99

SP - 48

EP - 54

JO - Experimental Eye Research

JF - Experimental Eye Research

SN - 0014-4835

ER -

ID: 128974982