Site 2 of the Yersinia pestis substrate-binding protein YfeA is a dynamic surface metal-binding site

Christopher D. Radka, Stephen G. Aller

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The substrate-binding protein YfeA (also known as YPO2439 or y1897) is a polyspecific metal-binding protein that is crucial for nutrient acquisition and virulence in Yersinia pestis, the causative microbe of plague. YfeA folds into a monomeric c-clamp like other substrate-binding proteins and has two metal-binding sites (sites 1 and 2). Site 2 is a bidentate surface site capable of binding Zn and Mn atoms and is a unique feature of YfeA. Occasionally, the site 2 residues of two YfeA molecules will cooperate with the histidine tag of a third YfeA molecule in coordinating the same metal and lead to metal-dependent crystallographic packing. Here, three crystal structures of YfeA are presented at 1.85, 2.05 and 2.25 Å resolution. A comparison of the structures reveals that the metal can be displaced at five different locations ranging from ∼4 to ∼16 Å away from the canonical site 2. These observations reveal different configurations of site 2 that enable cooperative metal binding and demonstrate how site 2 is dynamic and freely available for inter-protein metal coordination.

Original languageEnglish
Pages (from-to)286-293
Number of pages8
JournalActa Crystallographica Section F:Structural Biology Communications
StatePublished - Sep 1 2021

Bibliographical note

Funding Information:
Author contributions are as follows. Conceptualization, CDR and SGA; methodology, CDR and SGA; formal analysis, CDR and SGA; investigation, CDR; resources, SGA; writing – original draft preparation, CDR; writing – review and editing, CDR and SGA; visualization, CDR; supervision, SGA. All authors have read and agreed to the published version of the manuscript. The data for YfeA site 2 inter-coordinated structure 1 were collected on beamline CMCF-BM at the Canadian Light Source (CLS; Fodje et al., 2014), a national research facility of the University of Saskatchewan, which is supported by the Canada Foundation for Innovation (CFI), the Natural Sciences and Engineering Research Council (NSERC), the National Research Council (NRC), the Canadian Institutes of Health Research (CIHR), the Government of Saskatchewan and the University of Saskatchewan. The date for YfeA site 2 inter-coordinated structure 2 and structure 3 data were collected on the Southeast Regional Collaborative Access Team (SER-CAT) 22-ID beamline at the Advanced Photon Source, Argonne National Laboratory (ANL). SER-CAT is supported by its member institutions and equipment grants (S10_RR25528, S10_RR028976 and S10_OD027000) from the National Institutes of Health. Use of the APS was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. W-31-109-Eng-38. The authors declare that they have no conflicts of interest with the contents of this article.

Funding Information:
CDR was funded by the University of Alabama at Birmingham Office of Diversity, Equity, and Inclusion.

Publisher Copyright:
© 2021.


  • Crystallography
  • Inter-protein metal coordination
  • Manganese
  • Plague
  • Substrate-binding proteins
  • Transition-metal homeostasis
  • Yersinia pestis
  • YfeA site 2
  • Zinc

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Condensed Matter Physics


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