8DOR

Crystal structure of Dihydropteridine reductase/oxygen-insensitive NAD(P)H nitroreductase from Klebsiella pneumoniae

Summary for 8DOR

• Entry DOI: 10.2210/pdb8dor/pdb
• Descriptor: Dihydropteridine reductase/oxygen-insensitive NAD(P)H nitroreductase, FLAVIN MONONUCLEOTIDE, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: ssgcid, structural genomics, seattle structural genomics center for infectious disease, oxidoreductase
• Biological source: Klebsiella pneumoniae
• Total number of polymer chains: 4
• Total formula weight: 102962.83

Authors

Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2022-07-14, release date: 2022-07-27, Last modification date: 2024-08-21)

Primary citation

Kancherla, A.D.,Liu, L.,Tillery, L.,Shek, R.,Craig, J.K.,Machen, A.J.,Seibold, S.,Battaile, K.P.,Fradi, S.,Barrett, L.K.,Subramanian, S.,Myler, P.,Van Voorhis, W.C.,Lovell, S.
Crystal structures of NAD(P)H nitroreductases from Klebsiella pneumoniae.
Acta Crystallogr.,Sect.F, 80:173-182, 2024

PubMed Abstract: 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.

PubMed: 38990055
DOI: 10.1107/S2053230X24006472

Experimental method

X-RAY DIFFRACTION (1.35 Å)