4HMQ

Crystal structure of streptococcus pneumoniae TIGR4 PiaA in complex with ferrichrome

Summary for 4HMQ

• Entry DOI: 10.2210/pdb4hmq/pdb
• Related: 4HMO 4HMP
• Descriptor: Iron-compound ABC transporter, iron compound-binding protein, FERRICHROME, CADMIUM ION, ... (7 entities in total)
• Functional Keywords: class iii substrate binding protein, alpha and beta protein, periplasmic binding protein type iii fold, iron uptake abc transporter system substrate binding protein, hydroxamate siderophore, membrane anchored lipoprotein, transport protein
• Biological source: Streptococcus pneumoniae
• Total number of polymer chains: 2
• Total formula weight: 77456.17

Authors

Cheng, W.,Li, Q.,Jiang, Y.-L.,Chen, Y.,Zhou, C.-Z. (deposition date: 2012-10-18, release date: 2013-09-04, Last modification date: 2024-03-20)

Primary citation

Cheng, W.,Li, Q.,Jiang, Y.-L.,Zhou, C.-Z.,Chen, Y.
Structures of Streptococcus pneumoniae PiaA and Its Complex with Ferrichrome Reveal Insights into the Substrate Binding and Release of High Affinity Iron Transporters
Plos One, 8:e71451-e71451, 2013

PubMed Abstract: Iron scarcity is one of the nutrition limitations that the Gram-positive infectious pathogens Streptococcus pneumoniae encounter in the human host. To guarantee sufficient iron supply, the ATP binding cassette (ABC) transporter Pia is employed to uptake iron chelated by hydroxamate siderophore, via the membrane-anchored substrate-binding protein PiaA. The high affinity towards ferrichrome enables PiaA to capture iron at a very low concentration in the host. We presented here the crystal structures of PiaA in both apo and ferrichrome-complexed forms at 2.7 and 2.1 Å resolution, respectively. Similar to other class III substrate binding proteins, PiaA is composed of an N-terminal and a C-terminal domain bridged by an α-helix. At the inter-domain cleft, a molecule of ferrichrome is stabilized by a number of highly conserved residues. Upon ferrichrome binding, two highly flexible segments at the entrance of the cleft undergo significant conformational changes, indicating their contribution to the binding and/or release of ferrichrome. Superposition to the structure of Escherichia coli ABC transporter BtuF enabled us to define two conserved residues: Glu119 and Glu262, which were proposed to form salt bridges with two arginines of the permease subunits. Further structure-based sequence alignment revealed that the ferrichrome binding pattern is highly conserved in a series of PiaA homologs encoded by both Gram-positive and negative bacteria, which were predicted to be sensitive to albomycin, a sideromycin antibiotic derived from ferrichrome.

PubMed: 23951167
DOI: 10.1371/journal.pone.0071451

Experimental method

X-RAY DIFFRACTION (2.1 Å)