Crystal Structure and Conformational Dynamics of Pyrococcus furiosus Prolyl Oligopeptidase.
Journal
Biochemistry
ISSN: 1520-4995
Titre abrégé: Biochemistry
Pays: United States
ID NLM: 0370623
Informations de publication
Date de publication:
26 03 2019
26 03 2019
Historique:
pubmed:
21
2
2019
medline:
14
1
2020
entrez:
21
2
2019
Statut:
ppublish
Résumé
Enzymes in the prolyl oligopeptidase family possess unique structures and substrate specificities that are important for their biological activity and for potential biocatalytic applications. The crystal structures of Pyrococcus furiosus ( Pfu) prolyl oligopeptidase (POP) and the corresponding S477C mutant were determined to 1.9 and 2.2 Å resolution, respectively. The wild type enzyme crystallized in an open conformation, indicating that this state is readily accessible, and it contained bound chloride ions and a prolylproline ligand. These structures were used as starting points for molecular dynamics simulations of Pfu POP conformational dynamics. The simulations showed that large-scale domain opening and closing occurred spontaneously, providing facile substrate access to the active site. Movement of the loop containing the catalytically essential histidine into a conformation similar to those found in structures with fully formed catalytic triads also occurred. This movement was modulated by chloride binding, providing a rationale for experimentally observed activation of POP peptidase catalysis by chloride. Thus, the structures and simulations reported in this study, combined with existing biochemical data, provide a number of insights into POP catalysis.
Identifiants
pubmed: 30786206
doi: 10.1021/acs.biochem.9b00031
pmc: PMC6714975
mid: NIHMS1021603
doi:
Substances chimiques
Archaeal Proteins
0
Serine Endopeptidases
EC 3.4.21.-
Prolyl Oligopeptidases
EC 3.4.21.26
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1616-1626Subventions
Organisme : NIGMS NIH HHS
ID : P30 GM124165
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103403
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR029205
Pays : United States
Références
J Chem Theory Comput. 2013 Aug 13;9(8):
pubmed: 24223528
Bioorg Med Chem Lett. 2008 Aug 1;18(15):4360-3
pubmed: 18606544
Cell Mol Life Sci. 2002 Feb;59(2):349-62
pubmed: 11915948
Chembiochem. 2015 Sep 7;16(13):1880-1883
pubmed: 26097041
Curr Protein Pept Sci. 2008 Feb;9(1):96-107
pubmed: 18336325
J Biol Chem. 2001 Sep 7;276(36):33518-25
pubmed: 11432860
J Am Chem Soc. 2008 Nov 19;130(46):15361-73
pubmed: 18939839
Nat Chem. 2018 Mar;10(3):318-324
pubmed: 29461523
J Comput Chem. 2008 Aug;29(11):1859-65
pubmed: 18351591
Biophys J. 2015 Jan 6;108(1):116-25
pubmed: 25564858
Protein Eng Des Sel. 2008 Dec;21(12):699-707
pubmed: 18836204
J Chem Theory Comput. 2011 Feb 8;7(2):525-37
pubmed: 26596171
J Bacteriol. 1997 Jun;179(11):3613-8
pubmed: 9171407
Protein Eng. 1992 Apr;5(3):197-211
pubmed: 1409539
Proteins. 2007 Nov 15;69(3):633-43
pubmed: 17623862
Chembiochem. 2009 Nov 23;10(17):2736-9
pubmed: 19798721
Science. 1971 Aug 27;173(3999):827-9
pubmed: 5572174
FEBS Lett. 2006 Jun 12;580(14):3493-7
pubmed: 16714022
J Phys Chem B. 1998 Apr 30;102(18):3586-616
pubmed: 24889800
Nat Protoc. 2007;2(4):924-32
pubmed: 17446874
Microbiol Mol Biol Rev. 2001 Mar;65(1):1-43
pubmed: 11238984
J Chem Phys. 2005 Feb 1;122(5):54101
pubmed: 15740304
Chem Soc Rev. 2012 Mar 7;41(5):1665-76
pubmed: 21975514
Methods Enzymol. 2001;330:445-54
pubmed: 11210523
BMC Genomics. 2014 Nov 18;15:985
pubmed: 25407321
PLoS One. 2013 Nov 12;8(11):e79349
pubmed: 24265767
Proteins. 2014 Jul;82(7):1428-43
pubmed: 24500901
Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3599-604
pubmed: 15738423
Cell Biochem Biophys. 2006;44(3):349-65
pubmed: 16679522
J Biol Chem. 2001 Jun 1;276(22):19310-7
pubmed: 11278687
PLoS One. 2011;6(11):e26251
pubmed: 22132071
Biochim Biophys Acta. 2013 Jan;1834(1):98-111
pubmed: 22940581
Chembiochem. 2016 May 17;17(10):913-7
pubmed: 26918396
J Biol Chem. 2001 Jan 12;276(2):1262-6
pubmed: 11031266
Chembiochem. 2011 Dec 16;12(18):2737-9
pubmed: 22069228
Biochimie. 2012 Jun;94(6):1398-411
pubmed: 22484394
J Biol Chem. 2010 Jul 9;285(28):21487-95
pubmed: 20444688
Cell. 1998 Jul 24;94(2):161-70
pubmed: 9695945
J Phys Chem B. 2010 Jun 17;114(23):7830-43
pubmed: 20496934
J Chem Theory Comput. 2013 Jan 8;9(1):461-469
pubmed: 23316124
J Chem Theory Comput. 2011 Jun 14;7(6):1583-94
pubmed: 26596426
J Chem Theory Comput. 2012 Sep 11;8(9):3257-3273
pubmed: 23341755