Dynamics-function relationship in the catalytic domains of N-terminal acetyltransferases.
Acetylation
Ligand specificity
N-terminal acetyltransferases
Normal modes analysis
Protein dynamics
Journal
Computational and structural biotechnology journal
ISSN: 2001-0370
Titre abrégé: Comput Struct Biotechnol J
Pays: Netherlands
ID NLM: 101585369
Informations de publication
Date de publication:
2020
2020
Historique:
received:
15
11
2019
revised:
14
02
2020
accepted:
25
02
2020
entrez:
25
3
2020
pubmed:
25
3
2020
medline:
25
3
2020
Statut:
epublish
Résumé
N-terminal acetyltransferases (NATs) belong to the superfamily of acetyltransferases. They are enzymes catalysing the transfer of an acetyl group from acetyl coenzyme A to the N-terminus of polypeptide chains. N-terminal acetylation is one of the most common protein modifications. To date, not much is known on the molecular basis for the exclusive substrate specificity of NATs. All NATs share a common fold called GNAT. A characteristic of NATs is the β6β7 hairpin loop covering the active site and forming with the α1α2 loop a narrow tunnel surrounding the catalytic site in which cofactor and polypeptide meet and exchange an acetyl group. We investigated the dynamics-function relationships of all available structures of NATs covering the three domains of Life. Using an elastic network model and normal mode analysis, we found a common dynamics pattern conserved through the GNAT fold; a rigid V-shaped groove formed by the β4 and β5 strands and splitting the fold in two dynamical subdomains. Loops α1α2, β3β4 and β6β7 all show clear displacements in the low frequency normal modes. We characterized the mobility of the loops and show that even limited conformational changes of the loops along the low-frequency modes are able to significantly change the size and shape of the ligand binding sites. Based on the fact that these movements are present in most low-frequency modes, and common to all NATs, we suggest that the α1α2 and β6β7 loops may regulate ligand uptake and the release of the acetylated polypeptide.
Identifiants
pubmed: 32206212
doi: 10.1016/j.csbj.2020.02.017
pii: S2001-0370(19)30521-5
pmc: PMC7078549
doi:
Types de publication
Journal Article
Langues
eng
Pagination
532-547Informations de copyright
© 2020 The Authors.
Déclaration de conflit d'intérêts
None.
Références
Nucleic Acids Res. 2013 Jan;41(Database issue):D344-7
pubmed: 23161676
Mol Cell. 2019 Mar 21;73(6):1097-1114
pubmed: 30878283
Nucleic Acids Res. 2014 Jan;42(Database issue):D310-4
pubmed: 24293656
J Struct Funct Genomics. 2010 Jun;11(2):167-80
pubmed: 20419351
Curr Opin Struct Biol. 2000 Apr;10(2):165-9
pubmed: 10753809
Hum Mol Genet. 2015 Apr 1;24(7):1956-76
pubmed: 25489052
J Am Chem Soc. 2014 Jun 18;136(24):8669-76
pubmed: 24836640
Protein Sci. 2008 Oct;17(10):1781-90
pubmed: 18596200
Structure. 2016 Jul 6;24(7):1044-56
pubmed: 27320834
PLoS Comput Biol. 2012;8(9):e1002705
pubmed: 23028297
Structure. 2017 Apr 4;25(4):641-649.e3
pubmed: 28380339
PLoS Comput Biol. 2016 Mar 25;12(3):e1004834
pubmed: 27015412
Structure. 2009 Mar 11;17(3):335-44
pubmed: 19278648
Curr Opin Struct Biol. 2018 Jun;50:75-81
pubmed: 29287233
Proc Natl Acad Sci U S A. 2009 May 19;106(20):8157-62
pubmed: 19420222
Structure. 2007 May;15(5):565-75
pubmed: 17502102
Structure. 2005 Jun;13(6):893-904
pubmed: 15939021
Biochim Biophys Acta. 2015 May;1850(5):911-922
pubmed: 25267310
Bioinformatics. 2010 Mar 1;26(5):689-91
pubmed: 20061306
Proteomics. 2015 Jul;15(14):2426-35
pubmed: 25951519
Mol Cell Proteomics. 2011 May;10(5):M110.004580
pubmed: 21383206
Biophys J. 2003 Oct;85(4):2186-97
pubmed: 14507684
Cancer Res. 2006 Nov 15;66(22):10677-82
pubmed: 17108104
Mol Gen Genet. 1987 Oct;209(3):481-8
pubmed: 2828880
Methods Enzymol. 2004;383:66-93
pubmed: 15063647
Mol Cell. 2011 Oct 7;44(1):39-50
pubmed: 21981917
Bioinformatics. 2012 Oct 1;28(19):2431-40
pubmed: 22796957
Biochim Biophys Acta. 2014 Oct;1844(10):1790-7
pubmed: 25062911
Protein Sci. 2008 May;17(5):918-29
pubmed: 18369194
J Biol Chem. 2012 May 25;287(22):18249-61
pubmed: 22431724
Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4405-4410
pubmed: 29581307
Sci Rep. 2016 Aug 23;6:31425
pubmed: 27550639
BMC Struct Biol. 2009 Jul 10;9:45
pubmed: 19591676
BMC Bioinformatics. 2014 Dec 30;15:427
pubmed: 25547242
Mol Microbiol. 2007 Jun;64(6):1540-8
pubmed: 17511810
J Mol Biol. 2001 Aug 17;311(3):433-44
pubmed: 11492997
J Biol Chem. 2017 Oct 27;292(43):17626-17642
pubmed: 28887305
Oncogene. 2013 Jan 17;32(3):269-76
pubmed: 22391571
Structure. 2015 Feb 3;23(2):332-41
pubmed: 25619998
J Biol Chem. 2017 Apr 21;292(16):6821-6837
pubmed: 28196861
J Mol Biol. 2017 Dec 8;429(24):3863-3874
pubmed: 28987732
J Mol Biol. 2003 Sep 19;332(3):657-74
pubmed: 12963374
Nat Commun. 2016 Oct 06;7:12882
pubmed: 27708256
Sci Rep. 2016 Feb 10;6:21304
pubmed: 26861501
Nucleic Acids Res. 2017 Jan 4;45(D1):D289-D295
pubmed: 27899584
Nucleic Acids Res. 2016 Jan 4;44(D1):D385-95
pubmed: 26476444
Proteins. 1998 Nov 15;33(3):417-29
pubmed: 9829700
Eur J Hum Genet. 2015 May;23(5):602-9
pubmed: 25099252
Cancer Res. 2010 Jun 1;70(11):4422-32
pubmed: 20501853
Biophys J. 2015 Sep 15;109(6):1101-9
pubmed: 26143655
Phys Life Rev. 2013 Mar;10(1):1-26
pubmed: 23199577
Bioinformatics. 2018 Oct 15;34(20):3586-3588
pubmed: 29741570
PLoS One. 2012;7(12):e52642
pubmed: 23285125
J Biol Chem. 2011 Oct 21;286(42):37002-10
pubmed: 21900231
J Biol Chem. 2016 Sep 9;291(37):19462-73
pubmed: 27445332
Nat Commun. 2014 Nov 07;5:5176
pubmed: 25376646
J Am Chem Soc. 2006 Aug 2;128(30):9766-72
pubmed: 16866533
Sci Rep. 2015 Mar 02;5:8673
pubmed: 25728374
J Comput Chem. 2017 Jul 5;38(18):1622-1630
pubmed: 28470912
Chembiochem. 2016 Feb 2;17(3):214-7
pubmed: 26593285
Arch Biochem Biophys. 2005 Jan 1;433(1):212-26
pubmed: 15581578
Genes Cells. 2008 Nov;13(11):1171-83
pubmed: 19090811
Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):14652-7
pubmed: 23959863
J Chem Theory Comput. 2017 Jun 13;13(6):3031-3048
pubmed: 28430426
Proteins. 1991;11(3):205-17
pubmed: 1749773
Nat Commun. 2014 Jun 11;5:4070
pubmed: 24915882
Nucleic Acids Res. 2020 Jan 8;48(D1):D376-D382
pubmed: 31724711
Int J Biochem Cell Biol. 2009 Dec;41(12):2528-37
pubmed: 19695338
Proteins. 2006 Aug 15;64(3):559-74
pubmed: 16736488
J Mol Evol. 2014 Oct;79(3-4):130-42
pubmed: 25217382
J Biol Chem. 2005 Jun 10;280(23):22108-14
pubmed: 15817456
Structure. 2006 Aug;14(8):1241-9
pubmed: 16905098
Nat Struct Mol Biol. 2013 Sep;20(9):1098-105
pubmed: 23912279
Mol Gen Genet. 1989 Jun;217(2-3):289-93
pubmed: 2671655
PLoS Comput Biol. 2015 Nov 25;11(11):e1004578
pubmed: 26606374
Biopolymers. 2008;90(6):751-8
pubmed: 18844292
PLoS One. 2013;8(4):e59004
pubmed: 23565140
Biochim Biophys Acta. 2016 Oct;1864(10):1372-401
pubmed: 27296530
J Biol Chem. 1996 Aug 2;271(31):18920-4
pubmed: 8702554
ACS Chem Biol. 2013;8(6):1121-7
pubmed: 23557624
Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4399-4404
pubmed: 29581253
Mol Biol Evol. 2019 Sep 1;36(9):2053-2068
pubmed: 31028708
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4
pubmed: 24753421
Gene. 2015 Aug 10;567(2):103-31
pubmed: 25987439