دورية أكاديمية
أعرض في EDS

Structure and mechanism of a phage-encoded SAM lyase revises catalytic function of enzyme family.

التفاصيل البيبلوغرافية
العنوان: Structure and mechanism of a phage-encoded SAM lyase revises catalytic function of enzyme family.
المؤلفون: Guo X; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden., Söderholm A; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden., Kanchugal P S; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden., Isaksen GV; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.; Hylleraas Centre for Quantum Molecular Sciences, Department of Chemistry, UiT - The Arctic University of Norway, Tromsø, Norway., Warsi O; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden., Eckhard U; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden., Trigüis S; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden., Gogoll A; Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden., Jerlström-Hultqvist J; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden., Åqvist J; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden., Andersson DI; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden., Selmer M; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
المصدر: ELife [Elife] 2021 Feb 10; Vol. 10. Date of Electronic Publication: 2021 Feb 10.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Bacteriophage T3/*genetics , Lyases/*genetics , Viral Proteins/*genetics, Bacteriophage T3/metabolism ; Escherichia coli/virology ; Lyases/metabolism ; S-Adenosylmethionine/metabolism ; Viral Proteins/metabolism
مستخلص: The first S-adenosyl methionine (SAM) degrading enzyme (SAMase) was discovered in bacteriophage T3, as a counter-defense against the bacterial restriction-modification system, and annotated as a SAM hydrolase forming 5'-methyl-thioadenosine (MTA) and L-homoserine. From environmental phages, we recently discovered three SAMases with barely detectable sequence similarity to T3 SAMase and without homology to proteins of known structure. Here, we present the very first phage SAMase structures, in complex with a substrate analogue and the product MTA. The structure shows a trimer of alpha-beta sandwiches similar to the GlnB-like superfamily, with active sites formed at the trimer interfaces. Quantum-mechanical calculations, thin-layer chromatography, and nuclear magnetic resonance spectroscopy demonstrate that this family of enzymes are not hydrolases but lyases forming MTA and L-homoserine lactone in a unimolecular reaction mechanism. Sequence analysis and in vitro and in vivo mutagenesis support that T3 SAMase belongs to the same structural family and utilizes the same reaction mechanism.
Competing Interests: XG, AS, SK, GI, OW, UE, ST, AG, JJ, JÅ, DA, MS No competing interests declared
(© 2021, Guo et al.)
References: J Biotechnol. 2006 Feb 10;121(3):291-8. (PMID: 16150509)
J Biol Chem. 1959 Jan;234(1):87-92. (PMID: 13610898)
J Comput Aided Mol Des. 2013 Mar;27(3):221-34. (PMID: 23579614)
J Biol Inorg Chem. 2009 Jun;14(5):643-51. (PMID: 19437047)
Phys Rev A Gen Phys. 1985 Mar;31(3):1695-1697. (PMID: 9895674)
J Mol Biol. 1999 Dec 3;294(3):745-56. (PMID: 10610793)
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32. (PMID: 20124692)
Biochem Soc Trans. 2006 Apr;34(Pt 2):330-3. (PMID: 16545107)
Annu Rev Genet. 1991;25:585-627. (PMID: 1812816)
J Phys Chem B. 2009 May 7;113(18):6378-96. (PMID: 19366259)
J Virol. 1976 Jul;19(1):136-45. (PMID: 781304)
J Med Chem. 2004 Mar 25;47(7):1750-9. (PMID: 15027866)
Nucleic Acids Res. 2008 Apr;36(7):2295-300. (PMID: 18287115)
J Chromatogr Sci. 2005 Feb;43(2):104-5. (PMID: 15826370)
Nature. 1979 Mar 1;278(5699):30-4. (PMID: 763348)
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2256-68. (PMID: 15572779)
Nat Methods. 2009 Sep;6(9):651-3. (PMID: 19684596)
Nat Ecol Evol. 2018 Aug;2(8):1321-1330. (PMID: 29807996)
J Med Chem. 2006 Oct 19;49(21):6177-96. (PMID: 17034125)
J Chem Theory Comput. 2016 Jan 12;12(1):281-96. (PMID: 26584231)
J Biol Chem. 1958 Sep;233(3):631-3. (PMID: 13575426)
FEBS J. 2016 Feb;283(3):425-37. (PMID: 26527104)
J Med Chem. 2004 Mar 25;47(7):1739-49. (PMID: 15027865)
J Am Chem Soc. 1988 Mar 1;110(6):1657-66. (PMID: 27557051)
J Chem Phys. 2010 Apr 21;132(15):154104. (PMID: 20423165)
Methods Enzymol. 1983;94:231-4. (PMID: 6312267)
J Virol. 1970 Dec;6(6):750-3. (PMID: 4924627)
DNA Res. 2005;12(5):291-9. (PMID: 16769691)
Mol Microbiol. 2011 Jun;80(6):1464-78. (PMID: 21507083)
J Biol Chem. 1966 May 10;241(9):1995-2006. (PMID: 5946625)
J Comput Chem. 2011 May;32(7):1456-65. (PMID: 21370243)
J Biol Chem. 1964 Nov;239:3866-74. (PMID: 14257621)
Annu Rev Cell Dev Biol. 2015;31:473-496. (PMID: 26359776)
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5. (PMID: 10829079)
Nat Protoc. 2007;2(9):2212-21. (PMID: 17853878)
Protein Sci. 2019 Feb;28(2):454-463. (PMID: 30371978)
Biochemistry. 1983 Jun 7;22(12):2828-32. (PMID: 6871165)
J Chem Theory Comput. 2010 May 11;6(5):1509-19. (PMID: 26615687)
J Phys Chem A. 2017 Jan 19;121(2):505-514. (PMID: 28004936)
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501. (PMID: 20383002)
Mol Cell. 2002 Jan;9(1):187-94. (PMID: 11804597)
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):352-67. (PMID: 22505256)
J Biol Chem. 1959 Jul;234(7):1784-6. (PMID: 13672964)
J Am Chem Soc. 2009 Jun 10;131(22):7917-27. (PMID: 19453183)
Mol Microbiol. 1991 Jul;5(7):1593-7. (PMID: 1943695)
J Virol. 1967 Feb;1(1):57-63. (PMID: 4918233)
Curr Opin Chem Biol. 2016 Feb;30:52-60. (PMID: 26629854)
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674. (PMID: 19461840)
Nucleic Acids Res. 2003 Jul 1;31(13):3320-3. (PMID: 12824317)
Proc Natl Acad Sci U S A. 1964 Aug;52:292-7. (PMID: 14206593)
J Virol. 1975 Aug;16(2):453-5. (PMID: 1097737)
فهرسة مساهمة: Keywords: E. coli; S-adenosyl methionine; bacteriophage; biochemistry; chemical biology; lyase; molecular biophysics; structural biology
Local Abstract: [plain-language-summary] Bacteria can be infected by viruses known as bacteriophages. These viruses inject their genetic material into bacterial cells and use the bacteria’s own machinery to build the proteins they need to survive and infect other cells. To protect themselves, bacteria produce a molecule called S-adenosyl methionine, or SAM for short, which deposits marks on the bacteria’s DNA. These marks help the bacteria distinguish their own genetic material from the genetic material of foreign invaders: any DNA not bearing the mark from SAM will be immediately broken down by the bacterial cell. This system helps to block many types of bacteriophage infections, but not all. Some bacteriophages carry genes that code for enzymes called SAMases, which can break down SAM, switching off the bacteria’s defenses. The most well-known SAMase was first discovered in the 1960s in a bacteriophage called T3. Chemical studies of this SAMase suggested that it works as a 'hydrolase', meaning that it uses water to break SAM apart. New SAMases have since been discovered in bacteriophages from environmental water samples, which, despite being able to degrade SAM, are genetically dissimilar to one another and the SAMase in T3. This brings into question whether these enzymes all use the same mechanism to break SAM down. To gain a better understanding of how these SAMases work, Guo, Söderholm, Kanchugal, Isaksen et al. solved the crystal structure of one of the newly discovered enzymes called Svi3-3. This revealed three copies of the Svi3-3 enzyme join together to form a unit that SAM binds to at the border between two of the enzymes. Computer simulations of this structure suggested that Svi3-3 holds SAM in a position where it cannot interact with water, and that once in the grip of the SAMase, SAM instead reacts with itself and splits into two. Experiments confirmed these predictions for Svi3-3 and the other tested SAMases. Furthermore, the SAMase from bacteriophage T3 was also found to degrade SAM using the same mechanism. This shows that this group of SAMases are not hydrolases as originally thought, but in fact ‘lyases’: enzymes that break molecules apart without using water. These findings form a starting point for further investigations into how SAM lyases help bacteriophages evade detection. SAM has various different functions in other living organisms, and these lyases could be used to modulate the levels of SAM in future studies investigating its role.
المشرفين على المادة: 0 (Viral Proteins)
7LP2MPO46S (S-Adenosylmethionine)
EC 4.- (Lyases)
تواريخ الأحداث: Date Created: 20210210 Date Completed: 20220201 Latest Revision: 20220201
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7877911
DOI: 10.7554/eLife.61818
PMID: 33567250
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.61818