دورية أكاديمية
Crystal structures of NAD(P)H nitroreductases from Klebsiella pneumoniae.
العنوان: | Crystal structures of NAD(P)H nitroreductases from Klebsiella pneumoniae. |
---|---|
المؤلفون: | Kancherla AD; Division of Allergy and Infectious Diseases, Center for Emerging and Re-emerging Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98109, USA., Liu L; Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA 98109, USA., Tillery L; Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA 98109, USA., Shek R; Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA 98109, USA., Craig JK; Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA 98109, USA., Machen AJ; Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA 98109, USA., Seibold S; Protein Structure and X-ray Crystallography Laboratory, University of Kansas, 2034 Becker Drive, Lawrence, KS 66047, USA., Battaile KP; NYX, New York Structural Biology Center, Upton, NY 10027, USA., Fradi S; Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA 98109, USA., Barrett LK; Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA 98109, USA., Subramanian S; Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA 98109, USA., Myler P; Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA 98109, USA., Van Voorhis WC; Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA 98109, USA., Lovell S; Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA 98109, USA. |
المصدر: | Acta crystallographica. Section F, Structural biology communications [Acta Crystallogr F Struct Biol Commun] 2024 Aug 01; Vol. 80 (Pt 8), pp. 173-182. Date of Electronic Publication: 2024 Jul 11. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: John Wiley & Sons Inc Country of Publication: United States NLM ID: 101620319 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2053-230X (Electronic) Linking ISSN: 2053230X NLM ISO Abbreviation: Acta Crystallogr F Struct Biol Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Malden, MA : John Wiley & Sons Inc., [2014]- |
مواضيع طبية MeSH: | Klebsiella pneumoniae*/enzymology , Nitroreductases*/chemistry , Nitroreductases*/metabolism , Models, Molecular*, Crystallography, X-Ray ; Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Bacterial Proteins/genetics ; Amino Acid Sequence ; Flavin Mononucleotide/metabolism ; Flavin Mononucleotide/chemistry ; Binding Sites ; Protein Binding ; Escherichia coli/metabolism ; Escherichia coli/genetics ; Escherichia coli/enzymology ; Protein Conformation, beta-Strand ; Recombinant Proteins/chemistry ; Recombinant Proteins/metabolism ; Recombinant Proteins/genetics |
مستخلص: | Klebsiella pneumoniae (Kp) is an infectious disease pathogen that poses a significant global health threat due to its potential to cause severe infections and its tendency to exhibit multidrug resistance. Understanding the enzymatic mechanisms of the oxygen-insensitive nitroreductases (Kp-NRs) from Kp is crucial for the development of effective nitrofuran drugs, such as nitrofurantoin, that can be activated as antibiotics. In this paper, three crystal structures of two Kp-NRs (PDB entries 7tmf/7tmg and 8dor) are presented, and an analysis of their crystal structures and their flavin mononucleotide (FMN)-binding mode is provided. The structures with PDB codes 7tmf (Kp-NR1a), 7tmg (Kp-NR1b) and 8dor (Kp-NR2) were determined at resolutions of 1.97, 1.90 and 1.35 Å, respectively. The Kp-NR1a and Kp-NR1b structures adopt an αβ fold, in which four-stranded antiparallel β-sheets are surrounded by five helices. With domain swapping, the β-sheet was expanded with a β-strand from the other molecule of the dimer. The difference between the structures lies in the loop spanning Leu173-Ala185: in Kp-NR1a the loop is disordered, whereas the loop adopts multiple conformations in Kp-NR1b. The FMN interactions within Kp-NR1/NR2 involve hydrogen-bond and π-stacking interactions. Kp-NR2 contains four-stranded antiparallel β-sheets surrounded by eight helices with two short helices and one β-sheet. Structural and sequence alignments show that Kp-NR1a/b and Kp-NR2 are homologs of the Escherichia coli oxygen-insensitive NRs YdjA and NfnB and of Enterobacter cloacae NR, respectively. By homology inference from E. coli, Kp-NR1a/b and Kp-NR2 may detoxify polynitroaromatic compounds and Kp-NR2 may activate nitrofuran drugs to cause bactericidal activity through a ping-pong bi-bi mechanism, respectively. |
References: | Infect Disord Drug Targets. 2009 Nov;9(5):493-506. (PMID: 19594426) FEMS Microbiol Rev. 2008 May;32(3):474-500. (PMID: 18355273) J Biol Chem. 2002 Mar 29;277(13):11513-20. (PMID: 11805110) J Biol Chem. 1979 May 25;254(10):4009-14. (PMID: 374406) J Mol Biol. 1970 Mar;48(3):443-53. (PMID: 5420325) J Biol Chem. 1991 Mar 5;266(7):4119-25. (PMID: 1999405) BMC Bioinformatics. 2006 Jul 12;7:339. (PMID: 16836757) J Bacteriol. 2012 Apr;194(7):1841-2. (PMID: 22408243) Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):293-302. (PMID: 21460447) J Biol Chem. 2005 Apr 8;280(14):13256-64. (PMID: 15684426) J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674. (PMID: 19461840) J Bacteriol. 1998 Nov;180(21):5529-39. (PMID: 9791100) Cancer Res. 1971 Dec;31(12):2184-8. (PMID: 4941089) Protein Expr Purif. 2005 May;41(1):207-34. (PMID: 15915565) FEBS Lett. 2022 Sep;596(18):2425-2440. (PMID: 35648111) J Appl Crystallogr. 2017 Sep 05;50(Pt 5):1352-1358. (PMID: 29021733) Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2288-94. (PMID: 15572783) Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):282-92. (PMID: 21460446) Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21. (PMID: 20057044) J Bacteriol. 1970 Dec;104(3):1126-34. (PMID: 16559085) J Mol Biol. 2008 Mar 14;377(1):258-67. (PMID: 18241886) Antimicrob Agents Chemother. 2019 Oct 22;63(11):. (PMID: 31481448) Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501. (PMID: 20383002) J Mol Biochem. 2012;1(2):76-85. (PMID: 27882309) J Antimicrob Chemother. 2018 Nov 1;73(11):2916-2926. (PMID: 30184207) Biology (Basel). 2021 May 01;10(5):. (PMID: 34062712) Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32. (PMID: 20124692) J Mol Biol. 1998 Jul 10;280(2):259-73. (PMID: 9654450) Biochemistry. 1996 Oct 22;35(42):13531-9. (PMID: 8885832) Environ Pollut. 2023 Jul 15;329:121718. (PMID: 37105464) |
معلومات مُعتمدة: | 75N93022C00036 United States AI NIAID NIH HHS |
فهرسة مساهمة: | Keywords: Klebsiella pneumoniae; SSGCID; Seattle Structural Genomics Center for Infectious Disease; nitroreductases; oxidoreductases; structural genomics |
المشرفين على المادة: | EC 1.7.- (Nitroreductases) 0 (Bacterial Proteins) 7N464URE7E (Flavin Mononucleotide) 0 (Recombinant Proteins) |
تواريخ الأحداث: | Date Created: 20240711 Date Completed: 20240805 Latest Revision: 20240807 |
رمز التحديث: | 20240807 |
مُعرف محوري في PubMed: | PMC11299736 |
DOI: | 10.1107/S2053230X24006472 |
PMID: | 38990055 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2053-230X |
---|---|
DOI: | 10.1107/S2053230X24006472 |