PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Community-Nominated Targets
July 2015
Drug Discovery: Solving the Structure of an Anti-hypertension Drug Target
July 2015
Retrospective: 7,000 Structures Closer to Understanding Biology
July 2015
Design and Evolution: Unveiling Translocator Proteins
June 2015
Signaling with DivL
May 2015
Signaling: A Platform for Opposing Functions
May 2015
Signaling: Securing Lipid-Protein Partnership
May 2015
Dynamic DnaK
March 2015
Iron-Sulfur Cluster Biosynthesis
December 2014
Mitochondrion: Flipping for UCP2
December 2014
Mitochondrion: Setting a New TRAP1
December 2014
Power in Numbers
August 2014
Quorum Sensing: A Groovy New Component
August 2014
Quorum Sensing: E. coli Gets Involved
August 2014
iTRAQing the Ubiquitinome
July 2014
Microbiome: The Dynamics of Infection
September 2013
Protein-Nucleic Acid Interaction: A Modified SAM to Modify tRNA
July 2013
Protein-Nucleic Acid Interaction: Versatile Glutamate
July 2013
PDZ Domains
April 2013
Alpha-Catenin Connections
March 2013
Cell-Cell Interaction: A FERM Connection
March 2013
Cell-Cell Interaction: Magic Structure from Microcrystals
March 2013
Cell-Cell Interaction: Modulating Self Recognition Affinity
March 2013
Bacterial Hemophores
January 2013
Archaeal Lipids
December 2012
Membrane Proteome: Capturing Multiple Conformations
December 2012
Lethal Tendencies
October 2012
Symmetry from Asymmetry
October 2012
A signal sensing switch
September 2012
Regulatory insights
September 2012
AlkB Homologs
August 2012
Budding ensemble
August 2012
Targeting Enzyme Function with Structural Genomics
July 2012
The machines behind the spindle assembly checkpoint
June 2012
Chaperone interactions
April 2012
Pilus Assembly Protein TadZ
April 2012
Revealing the Nuclear Pore Complex
March 2012
Topping off the proteasome
March 2012
Twist to open
March 2012
Disordered Proteins
February 2012
Analyzing an allergen
January 2012
Making Lipopolysaccharide
January 2012
Pulling on loose ends
January 2012
Terminal activation
December 2011
The Perils of Protein Secretion
November 2011
Bacterial Armor
October 2011
TLR4 regulation: heads or tails?
October 2011
Ribose production on demand
September 2011
Moving some metal
August 2011
Looking for lipids
July 2011
Ribofuranosyl Binding Protein
June 2011
A molecular switch for neuronal growth
May 2011
Cell wall recycler
May 2011
Added benefits
April 2011
NMR challenges current protein hydration dogma
March 2011
Nitrile Reductase QueF
March 2011
Tip formin
March 2011
Inhibiting factor
February 2011
PASK staying active
February 2011
Tryptophanyl-tRNA Synthetase
February 2011
Regulating nitrogen assimilation
January 2011
Subtle shifts
January 2011
December 2010
Function following form
October 2010
tRNA Isopentenyltransferase MiaA
August 2010
Importance of extension for integrin
June 2010
April 2010
Alg13 Subunit of N-Acetylglucosamine Transferase
February 2010
Hemolysin BL
January 2010
December 2009
Two-component signaling
December 2009
Network coverage
November 2009
Pseudouridine Synthase TruA
November 2009
Unusual cell division
October 2009
Toxin-antitoxin VapBC-5
September 2009
Salicylic Acid Binding Protein 2
August 2009
Proofreading RNA
July 2009
Ykul structure solves bacterial signaling puzzle
July 2009
Hda and DNA Replication
June 2009
Controlling p53
May 2009
Mitotic checkpoint control
May 2009
Ribonuclease and Ribonuclease Inhibitor
April 2009
The elusive helicase
April 2009
March 2009
High-energy storage system
February 2009
A new class of bacterial E3 ubiquitination enzymes
January 2009
Poly(A) RNA recognition
January 2009
Activating BAX
December 2008
Scavenger Decapping Enzyme DcpS
November 2008
Bacteriophage Lambda cII Protein
October 2008
New metal-binding domain
October 2008
Blocking AmtB
September 2008
September 2008
Aspartate Dehydrogenase
August 2008
RNase T
July 2008
May 2008

Research Themes Cell biology

Bacterial Hemophores

SBKB [doi:10.3942/psi_sgkb/fm_2013_1]
Featured System - January 2013
Short description: PSI biology researchers are exploring the proteins that pathogenic bacteria use to gather scarce heme groups, and the iron ions they carry.

Our bodies are filled with iron: iron in hemoglobin colors our blood bright red and iron is used as a chemical tool in many cellular proteins. Altogether, we have several grams of iron scattered through our cells. Surprisingly, however, lack of iron often limits the growth of pathogenic bacteria infecting our bodies. This is by design: our bodies have evolved to guard their store of iron, so the amount of free iron circulating through the body is vanishingly small. As you might expect, however, bacteria have evolved methods to fight back and obtain the iron that is essential for their growth.


70% of our iron is found in hemoglobin, which carries oxygen in our red blood cells. This iron is bound tightly in heme, a small, planar molecule that holds the iron ion at its center. Bacteria have developed an elaborate system for gathering this hemoglobin-bound iron and delivering it into the bacterial cell. Hemophores, such as the one shown here from the bacterium that causes anthrax (PDB entry 3sik), scavenge through the blood and extract heme groups from any hemoglobin that they find.

Mining for Iron

Hemophores are assisted by a variety of other proteins. In some bacteria, hemolysins are used to break red blood cells, releasing the hemoglobin. Hemophores then bind the hemoglobin and extract the heme, as shown here at the top (PDB entry 3szk). The hemophore then binds to specific receptors (shown in green) on the bacterial cell surface, which transport the heme inside (PDB entry 3csl). Finally, inside the cell, the heme may be used in bacterial heme proteins, or it may be broken down by heme oxygenases, which release the iron as they degrade the surrounding porphyrin. Several structures of these heme-degrading enzymes have been solved by PSI researchers. Two early structures from MCSG revealed dimeric enzymes with two active sites (PDB entries 1sqe and 1xbw, not shown here). A recent structure solved by researchers at UC4CDI shows a tuberculosis heme-degrading enzyme trapped in an unusual inactive conformation with two hemes in each of the active sites, revealing the extensive flexibility of the surrounding protein (PDB entry 3hx9, shown at the bottom).

Recognizing Heme

The structure of the anthrax hemophore, solved by researchers at UC4CDI (PDB entry 3sik), reveals a binding pocket that grips the heme group. Two amino acids lock the heme in place: one tyrosine coordinates directly with the iron atom and a second tyrosine strengthens the interaction by making the coordinating tyrosine more electronegative. To look at this interaction in more detail, the JSmol tab below displays an interactive JSmol.

Anthrax Hemophore (PDB entry 3sik)

The complex of an anthrax hemophore with heme is included in this structure. Two tyrosine amino acids, shown in bright turquoise, form a specific interaction with the iron atom in the heme (shown in red). Use the buttons to view the whole protein, and to display all of the atoms.


  1. Ekworomadu, M. T. et al. Differential function of lip residues in the mechanism and biology of an anthrax hemophore. PLoS Pathogens 8, e1002559 (2012).

  2. Kumar, K. K. et al. Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH. J. Biol. Chem. 286, 38439-38447 (2011).

  3. Chim, N., Iniguez, A., Nguyen, T. Q. & Goulding, C. W. Unusual diheme conformation of the heme-degrading protein from Mycobacterium tuberculosis. J. Mol. Biol. 395, 595- 608 (2010).

  4. Nairz, M., Schroll, A., Sonnweber, T. & Weiss, G. The struggle for iron - a metal at the host-pathogen interface. Cell. Microbio. 12, 1691-1702 (2010).

  5. Krieg, S. et al. Heme uptake across the outer membrane as revealed by crystal structures of the receptor-hemophore complex. Proc. Natl. Acad. Sci. USA 106, 1045-1050 (2009).

  6. Wu, R. et al. Staphylococcus aureus IsdG and IsdI, heme-degrading enzymes with structural similarity to monooxygenases. J. Biol. Chem. 280, 2840-2846 (2005).

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health