Structural analysis of molybdate binding protein ModA from Klebsiella pneumoniae.

Klebsiella pneumoniae, a facultative anaerobe, relies on acquiring molybdenum to sustain growth in anaerobic conditions, a crucial factor for the pathogen to establish infections within host environments. Molybdenum plays a critical role in pathogenesis as it forms an essential component of cofactors for molybdoenzymes. K. pneumoniae utilizes the ABC (ATP-Binding-Cassette) transporter encoded by the modABC operon for uptake of the group VI elements molybdenum and tungsten. In this study, we determined the X-ray crystal structures of both the molybdenum-free and molybdenum-bound substrate-binding protein (SBP) ModA from Klebsiella pneumoniae to 2.00 Å and 1.77 Å resolution respectively. ModA crystallizes in the space group P222 with a single monomer in one asymmetric unit. The purified protein remained soluble and specifically bound molybdate and tungstate with Kd values of 6.3 nM and 5.2 nM, respectively. Tungstate competes with molybdate by binding to ModA, resulting in enhanced antimicrobial activity. These data provide a starting point for structural and functional analyses of molybdate transport in K. pneumoniae.