6CN7

The structure of aerobactin synthetase IucC from a hypervirulent pathotype of Klebsiella pneumoniae

Summary for 6CN7

• Entry DOI: 10.2210/pdb6cn7/pdb
• Descriptor: Aerobactin synthase IucC, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID (3 entities in total)
• Functional Keywords: aerobactin, synthetase, ligase
• Biological source: Klebsiella pneumoniae
• Total number of polymer chains: 8
• Total formula weight: 528202.97

Authors

Bailey, D.C.,Rice, M.R.,Gulick, A.M. (deposition date: 2018-03-07, release date: 2018-04-11, Last modification date: 2023-10-04)

Primary citation

Bailey, D.C.,Alexander, E.,Rice, M.R.,Drake, E.J.,Mydy, L.S.,Aldrich, C.C.,Gulick, A.M.
Structural and functional delineation of aerobactin biosynthesis in hypervirulentKlebsiella pneumoniae.
J. Biol. Chem., 293:7841-7852, 2018

PubMed Abstract: Aerobactin, a citryl-hydroxamate siderophore, is produced by a number of pathogenic Gram-negative bacteria to aid in iron assimilation. Interest in this well-known siderophore was reignited by recent investigations suggesting that it plays a key role in mediating the enhanced virulence of a hypervirulent pathotype of (hvKP). In contrast to classical opportunistic strains of , hvKP causes serious life-threatening infections in previously healthy individuals in the community. Multiple contemporary reports have confirmed fears that the convergence of multidrug-resistant and hvKP pathotypes has led to the evolution of a highly transmissible, drug-resistant, and virulent "super bug." Despite hvKP harboring four distinct siderophore operons, knocking out production of aerobactin led to a significant attenuation of virulence. Herein, we continue our structural and functional studies on the biosynthesis of this crucial virulence factor. heterologous production and reconstitution of aerobactin biosynthesis from hvKP was carried out, demonstrating the specificity, stereoselectivity, and kinetic throughput of the complete pathway. Additionally, we present a steady-state kinetic analysis and the X-ray crystal structure of the second aerobactin synthetase IucC, as well as describe a surface entropy reduction strategy that was employed for structure determination. Finally, we show solution X-ray scattering data that support a unique dimeric quaternary structure for IucC. These new insights into aerobactin assembly will help inform potential antivirulence strategies and advance our understanding of siderophore biosynthesis.

PubMed: 29618511
DOI: 10.1074/jbc.RA118.002798

Experimental method

X-RAY DIFFRACTION (2.45 Å)