دورية أكاديمية
أعرض في EDS

Crystal structures of NAD(P)H nitroreductases from Klebsiella pneumoniae.

التفاصيل البيبلوغرافية
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.
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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
الوصف
تدمد:2053-230X
DOI:10.1107/S2053230X24006472