Ferric ion (hydr)oxo clusters in the “Venus flytrap” cleft of FbpA: Mössbauer, calorimetric and mass spectrometric studies

Mukherjee, Arindam; Bilton, Paul R.; Mackay, Logan; Janoschka, Adam; Zhu, Haizhong; Rea, Dean; Langridge‐Smith, Patrick R. R.; Campopiano, Dominic J.; Teschner, Thomas; Trautwein, Alfred X.; Schünemann, Volker; Sadler, Peter J.

doi:10.1007/s00775-012-0878-z

Cited by 3 publications

(1 citation statement)

References 47 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[19][20][21][22] Recently biochemical and X-ray crystallography studies by our group and others revealed that other metal ions including Hf 4+ , Zr 4+ and Ti 4+ as well as Fe 3+ when binding to FbpA, can assemble into the iron binding cleft by means of the oxo-metal clusters that could function with the known two-tyrosine motif (Tyr195 and Tyr196) as ligands, and the proteins were in an open conformation. [23][24][25][26][27][28][29][30] Therefore, it is premised that the binding of these Fe 3+ -like metal ions could either block iron binding to FbpA directly when competing with Fe 3+ , or alter the protein conformation to impede iron transport into the cytoplasmic membrane indirectly. FbpA could be served as a potential target for designing metallo-antibacterial drugs.…”

Section: Introductionmentioning

confidence: 99%

Binding of oxo-Cu2 clusters to ferric ion-binding protein A from Neisseria gonorrhoeae: a structural insight

Chen

Wang

et al. 2013

Metallomics

View full text Add to dashboard Cite

The ferric ion-binding protein A (FbpA), a member of transferrin superfamily, is a periplasmic iron transporter employed by many Gram-negative pathogens. Our experiments indicated copper(ii) could bind with Neisseria gonorrhoeae FbpA (NgFbpA), and the binding constant reached up to (8.7 ± 0.2) × 10(8) M(-1)via UV-vis titration. The crystal structure of recombinant Cu-NgFbpA at 2.1 Å revealed that the oxo-Cu2 clusters (dinuclear centres) assembled in the iron binding cleft and were bound to the two adjacent tyrosine residues (Y195 and Y196) of the protein, two Cu ions coordinated with two tyrosines, Y195 and Y196, respectively, which was different from the binding model of Fe ion with FbpA, in which Y195 and Y196 coordinated together with one Fe ion. While this was similar to the binding of Zr and Hf ion clusters, Y195 and Y196 coordinated with two metal ions and the μ-oxo-bridges linking the metal ions. Structural superimposition demonstrated that oxo-Cu2-NgFbpA still keeping an open conformation, similar to the apo-form of NgFbpA. The structure presented additional information towards an understanding of the function of FbpA, and provided a detailed binding model for FbpA protein with the possible metal ions in a biological system.

show abstract