Current status of PTMs structural databases: applications, limitations and prospects

doi:10.1007/s00726-021-03119-z

Review

. 2022 Apr;54(4):575-590.

doi: 10.1007/s00726-021-03119-z. Epub 2022 Jan 12.

Current status of PTMs structural databases: applications, limitations and prospects

Alexandre G de Brevern^{1

2

3}, Joseph Rebehmed⁴

Affiliations

¹ Université de Paris, INSERM, UMR_S 1134, DSIMB, 75739, Paris, France.
² Université de la Réunion, INSERM, UMR_S 1134, DSIMB, 97715, Saint-Denis de La Réunion, France.
³ Laboratoire d'Excellence GR-Ex, 75739, Paris, France.
⁴ Department of Computer Science and Mathematics, Lebanese American University, Beirut, Lebanon. joseph.rebehmed@lau.edu.lb.

PMID: 35020020
DOI: 10.1007/s00726-021-03119-z

Review

Current status of PTMs structural databases: applications, limitations and prospects

Alexandre G de Brevern et al. Amino Acids. 2022 Apr.

. 2022 Apr;54(4):575-590.

doi: 10.1007/s00726-021-03119-z. Epub 2022 Jan 12.

Authors

Alexandre G de Brevern^{1

2

3}, Joseph Rebehmed⁴

Affiliations

¹ Université de Paris, INSERM, UMR_S 1134, DSIMB, 75739, Paris, France.
² Université de la Réunion, INSERM, UMR_S 1134, DSIMB, 97715, Saint-Denis de La Réunion, France.
³ Laboratoire d'Excellence GR-Ex, 75739, Paris, France.
⁴ Department of Computer Science and Mathematics, Lebanese American University, Beirut, Lebanon. joseph.rebehmed@lau.edu.lb.

PMID: 35020020
DOI: 10.1007/s00726-021-03119-z

Abstract

Protein 3D structures, determined by their amino acid sequences, are the support of major crucial biological functions. Post-translational modifications (PTMs) play an essential role in regulating these functions by altering the physicochemical properties of proteins. By virtue of their importance, several PTM databases have been developed and released in decades, but very few of these databases incorporate real 3D structural data. Since PTMs influence the function of the protein and their aberrant states are frequently implicated in human diseases, providing structural insights to understand the influence and dynamics of PTMs is crucial for unraveling the underlying processes. This review is dedicated to the current status of databases providing 3D structural data on PTM sites in proteins. Some of these databases are general, covering multiple types of PTMs in different organisms, while others are specific to one particular type of PTM, class of proteins or organism. The importance of these databases is illustrated with two major types of in silico applications: predicting PTM sites in proteins using machine learning approaches and investigating protein structure-function relationships involving PTMs. Finally, these databases suffer from multiple problems and care must be taken when analyzing the PTMs data.

Keywords: Glycosylation; Modified amino acids; Phosphorylation; Prediction approaches; Protein structures; Secondary structures; Structure/function relationship.

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1. Aggarwal S, Banerjee SK, Talukdar NC, Yadav AK (2020) Post-translational modification crosstalk and hotspots in sirtuin interactors implicated in cardiovascular diseases. Front Genet 11:356. https://doi.org/10.3389/fgene.2020.00356 - DOI - PubMed - PMC
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[1] Adhikari S, Nice EC, Deutsch EW, Lane L, Omenn GS, Pennington SR, Paik YK, Overall CM, Corrales FJ, Cristea IM, Van Eyk JE, Uhlen M, Lindskog C, Chan DW, Bairoch A, Waddington JC, Justice JL, LaBaer J, Rodriguez H, He F, Kostrzewa M, Ping P, Gundry RL, Stewart P, Srivastava S, Srivastava S, Nogueira FCS, Domont GB, Vandenbrouck Y, Lam MPY, Wennersten S, Vizcaino JA, Wilkins M, Schwenk JM, Lundberg E, Bandeira N, Marko-Varga G, Weintraub ST, Pineau C, Kusebauch U, Moritz RL, Ahn SB, Palmblad M, Snyder MP, Aebersold R, Baker MS (2020) A high-stringency blueprint of the human proteome. Nat Commun 11(1):5301. https://doi.org/10.1038/s41467-020-19045-9 - DOI - PubMed - PMC

[2] Adhikari S, Nice EC, Deutsch EW, Lane L, Omenn GS, Pennington SR, Paik YK, Overall CM, Corrales FJ, Cristea IM, Van Eyk JE, Uhlen M, Lindskog C, Chan DW, Bairoch A, Waddington JC, Justice JL, LaBaer J, Rodriguez H, He F, Kostrzewa M, Ping P, Gundry RL, Stewart P, Srivastava S, Srivastava S, Nogueira FCS, Domont GB, Vandenbrouck Y, Lam MPY, Wennersten S, Vizcaino JA, Wilkins M, Schwenk JM, Lundberg E, Bandeira N, Marko-Varga G, Weintraub ST, Pineau C, Kusebauch U, Moritz RL, Ahn SB, Palmblad M, Snyder MP, Aebersold R, Baker MS (2020) A high-stringency blueprint of the human proteome. Nat Commun 11(1):5301. https://doi.org/10.1038/s41467-020-19045-9 - DOI - PubMed - PMC

[3] Aebersold R, Agar JN, Amster IJ, Baker MS, Bertozzi CR, Boja ES, Costello CE, Cravatt BF, Fenselau C, Garcia BA, Ge Y, Gunawardena J, Hendrickson RC, Hergenrother PJ, Huber CG, Ivanov AR, Jensen ON, Jewett MC, Kelleher NL, Kiessling LL, Krogan NJ, Larsen MR, Loo JA, Ogorzalek Loo RR, Lundberg E, MacCoss MJ, Mallick P, Mootha VK, Mrksich M, Muir TW, Patrie SM, Pesavento JJ, Pitteri SJ, Rodriguez H, Saghatelian A, Sandoval W, Schlüter H, Sechi S, Slavoff SA, Smith LM, Snyder MP, Thomas PM, Uhlén M, Van Eyk JE, Vidal M, Walt DR, White FM, Williams ER, Wohlschlager T, Wysocki VH, Yates NA, Young NL, Zhang B (2018) How many human proteoforms are there? Nat Chem Biol 14(3):206–214. https://doi.org/10.1038/nchembio.2576 - DOI - PubMed - PMC

[4] Aebersold R, Agar JN, Amster IJ, Baker MS, Bertozzi CR, Boja ES, Costello CE, Cravatt BF, Fenselau C, Garcia BA, Ge Y, Gunawardena J, Hendrickson RC, Hergenrother PJ, Huber CG, Ivanov AR, Jensen ON, Jewett MC, Kelleher NL, Kiessling LL, Krogan NJ, Larsen MR, Loo JA, Ogorzalek Loo RR, Lundberg E, MacCoss MJ, Mallick P, Mootha VK, Mrksich M, Muir TW, Patrie SM, Pesavento JJ, Pitteri SJ, Rodriguez H, Saghatelian A, Sandoval W, Schlüter H, Sechi S, Slavoff SA, Smith LM, Snyder MP, Thomas PM, Uhlén M, Van Eyk JE, Vidal M, Walt DR, White FM, Williams ER, Wohlschlager T, Wysocki VH, Yates NA, Young NL, Zhang B (2018) How many human proteoforms are there? Nat Chem Biol 14(3):206–214. https://doi.org/10.1038/nchembio.2576 - DOI - PubMed - PMC

[5] Aggarwal S, Banerjee SK, Talukdar NC, Yadav AK (2020) Post-translational modification crosstalk and hotspots in sirtuin interactors implicated in cardiovascular diseases. Front Genet 11:356. https://doi.org/10.3389/fgene.2020.00356 - DOI - PubMed - PMC

[6] Aggarwal S, Banerjee SK, Talukdar NC, Yadav AK (2020) Post-translational modification crosstalk and hotspots in sirtuin interactors implicated in cardiovascular diseases. Front Genet 11:356. https://doi.org/10.3389/fgene.2020.00356 - DOI - PubMed - PMC

[7] Ajit D, Trzeciakiewicz H, Tseng JH, Wander CM, Chen Y, Ajit A, King DP, Cohen TJ (2019) A unique tau conformation generated by an acetylation-mimic substitution modulates P301S-dependent tau pathology and hyperphosphorylation. J Biol Chem 294(45):16698–16711. https://doi.org/10.1074/jbc.RA119.009674 - DOI - PubMed - PMC

[8] Ajit D, Trzeciakiewicz H, Tseng JH, Wander CM, Chen Y, Ajit A, King DP, Cohen TJ (2019) A unique tau conformation generated by an acetylation-mimic substitution modulates P301S-dependent tau pathology and hyperphosphorylation. J Biol Chem 294(45):16698–16711. https://doi.org/10.1074/jbc.RA119.009674 - DOI - PubMed - PMC

[9] Ayyappan V, Wat R, Barber C, Vivelo CA, Gauch K, Visanpattanasin P, Cook G, Sazeides C, Leung AKL (2021) ADPriboDB 2.0: an updated database of ADP-ribosylated proteins. Nucleic Acids Res 49(D1):D261–D265. https://doi.org/10.1093/nar/gkaa941 - DOI - PubMed

[10] Ayyappan V, Wat R, Barber C, Vivelo CA, Gauch K, Visanpattanasin P, Cook G, Sazeides C, Leung AKL (2021) ADPriboDB 2.0: an updated database of ADP-ribosylated proteins. Nucleic Acids Res 49(D1):D261–D265. https://doi.org/10.1093/nar/gkaa941 - DOI - PubMed

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Current status of PTMs structural databases: applications, limitations and prospects

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Current status of PTMs structural databases: applications, limitations and prospects

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Abstract

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