Haem recognition by a <i>Staphylococcus aureus</i> NEAT domain

Grigg, J.C.; Vermeiren, Christie; Heinrichs, David E.; Murphy, M.E.P.

doi:10.1111/j.1365-2958.2006.05502.x

Cited by 144 publications

(261 citation statements)

References 43 publications

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“…1A). These absorp-tion features are consistent with the previous observation that the heme iron in IsdA is pentacoordinate (19,24).…”

Section: Resultssupporting

confidence: 81%

“…IsdA-hemin and IsdC-hemin complexes are pentacoordinate and use Tyr as their only axial ligand (19,20), whereas Shp-and HtsA-hemin complexes are hexacoordinate using two Met and Met/His residues as the axial ligands, respectively (15,18). The Tyr-hemin ligation may be a major factor for the higher hemin affinities of IsdA and IsdC.…”

Section: Kinetic Parametermentioning

confidence: 99%

“…The S. pyogenes system has a homologue in S. equi (9), whereas the homologue of the S. aureus system is present in B. anthracis (12). These surface proteins, but not Shp, contain the NEAr transporter (NEAT) domains (17), although the structure of the Shp heme-binding domain (18) is similar to that of the NEAT domains of IsdA (19) and IsdC (20).…”

mentioning

confidence: 97%

“…IsdH binds haptoglobin-hemoglobin, although it appears not to be critical for using methemoglobin hemin as an iron source in vitro (22). IsdA and the B. anthracis homologue of IsdC are also important for hemin uptake (12,19). IsdB, IsdA, and IsdC bind heme (11,19,20,23,24), and structural studies show that IsdA and IsdC bind hemin in a pentacoordinate complex with a tyrosine residue as the only axial ligand (19,20), in contrast to the hexacoordination of the heme iron in Shp and HtsA (14,15).…”

mentioning

confidence: 99%

“…IsdA and the B. anthracis homologue of IsdC are also important for hemin uptake (12,19). IsdB, IsdA, and IsdC bind heme (11,19,20,23,24), and structural studies show that IsdA and IsdC bind hemin in a pentacoordinate complex with a tyrosine residue as the only axial ligand (19,20), in contrast to the hexacoordination of the heme iron in Shp and HtsA (14,15). It has been proposed that IsdH and IsdB capture haptoglobin-hemoglobin and hemoglobin, respectively, and heme is transferred from bound hemoglobin to IsdA, then IsdC, and finally to ABC transporters IsdDEF and/or HtsABC (25,26).…”

mentioning

confidence: 99%

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Direct Hemin Transfer from IsdA to IsdC in the Iron-regulated Surface Determinant (Isd) Heme Acquisition System of Staphylococcus aureus

Liu

Tanaka

Zhu

et al. 2008

Journal of Biological Chemistry

108

147

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The iron-regulated surface determinants (Isd) of Staphylococcus aureus, including surface proteins IsdA, IsdB, IsdC, and IsdH and ATP-binding cassette transporter IsdDEF, constitute the machinery for acquiring heme as a preferred iron source. Here we report hemin transfer from hemin-containing IsdA (holo-IsdA) to hemin-free IsdC (apo-IsdC). The reaction has an equilibrium constant of 10 ؎ 5 at 22°C in favor of holo-IsdC formation. During the reaction, holo-IsdA binds to apo-IsdC and then transfers the cofactor to apo-IsdC with a rate constant of 54.3 ؎ 1.8 s ؊1 at 25°C. The transfer rate is >70,000 times greater than the rate of simple hemin dissociation from holoIsdA into solvent (k transfer ‫؍‬ 54.3 s ؊1 versus k ؊hemin ‫؍‬ 0.00076 s ؊1 ). The standard free energy change, ⌬G 0 , is ؊27 kJ/mol for the formation of the holo-IsdA-apo-IsdC complex. IsdC has a higher affinity for hemin than IsdA. These results indicate that the IsdA-to-IsdC hemin transfer is through the activated holoIsdA-apo-IsdC complex and is driven by the higher affinity of apo-IsdC for the cofactor. These findings demonstrate for the first time in the Isd system that heme transfer is rapid, direct, and affinity-driven from IsdA to IsdC. These results also provide the first example of heme transfer from one surface protein to another surface protein in Gram-positive bacteria and, perhaps most importantly, indicate that the mechanism of activated heme transfer, which we previously demonstrated between the streptococcal proteins Shp and HtsA, may apply in general to all bacterial heme transport systems.

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“…1A). These absorp-tion features are consistent with the previous observation that the heme iron in IsdA is pentacoordinate (19,24).…”

Section: Resultssupporting

confidence: 81%

Section: Kinetic Parametermentioning

confidence: 99%

mentioning

confidence: 97%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Direct Hemin Transfer from IsdA to IsdC in the Iron-regulated Surface Determinant (Isd) Heme Acquisition System of Staphylococcus aureus

Liu

Tanaka

Zhu

et al. 2008

Journal of Biological Chemistry

108

147

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Mycobacterium tuberculosis low molecular weight T‐cell antigen Mtb8.4 has heme‐binding and fiber‐forming properties

et al. 2022

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Mtb8.4, a secretory T‐cell antigen of Mycobacterium tuberculosis, is important for providing an antigen‐specific immune response. In this study, we showed Mtb8.4 to have both heme‐binding and fibril‐forming properties, using experimental and in silico methods. High absorbance at 410 nm and interaction with hemin‐agarose demonstrated its heme‐binding nature. Titration of Mtb8.4 with heme resulted in 1 : 1 stoichiometry. The heme‐binding pocket in Mtb8.4 was identified by molecular modeling, and binding residues were predicted using molecular docking. The molecular dynamics simulations of apo‐ and heme‐bound Mtb8.4 confirmed that the heme group forms a stable complex. Transmission electron microscopy analyses and dye‐binding assays showed that Mtb8.4 forms fibers. Computational studies predicted that the C‐terminal sequence (93AAQYIGLVESV103) is important for forming fibers. In silico analyses further anticipated the probable epitope (82AMAAQLQAV90) of Mtb8.4. The fiber‐forming properties of Mtb8.4 could be advantageous from a vaccine perspective for aggregate/fibril‐based vaccine delivery or it might influence the epitope presentation of Mtb8.4.

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Iron Acquisition by Bacillus anthracis

Pishchany

Skaar

2010

Bacillus Anthracis and Anthrax

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Haem recognition by a Staphylococcus aureus NEAT domain

Cited by 144 publications

References 43 publications

Direct Hemin Transfer from IsdA to IsdC in the Iron-regulated Surface Determinant (Isd) Heme Acquisition System of Staphylococcus aureus

Direct Hemin Transfer from IsdA to IsdC in the Iron-regulated Surface Determinant (Isd) Heme Acquisition System of Staphylococcus aureus

Mycobacterium tuberculosis low molecular weight T‐cell antigen Mtb8.4 has heme‐binding and fiber‐forming properties

Iron Acquisition by Bacillus anthracis

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