NDLI: Non-Heme-Binding Domains and Segments of the Staphylococcus aureus IsdB Protein Critically Contribute to the Kinetics and Equilibrium of Heme Acquisition from Methemoglobin

Content Provider	PubMed Central
Author	Zhu, Hui Li, Dengfeng Liu, Mengyao Valerie, Copié Lei, Benfang
Editor	Hung, Ton-that
Copyright Year	2014
Abstract	The hemoglobin receptor IsdB rapidly acquires heme from methemoglobin (metHb) in the heme acquisition pathway of Staphylococcus aureus. IsdB consists of N-terminal segment (NS), NEAT1 (N1), middle (MD), and heme binding NEAT2 (N2) domains, and C-terminal segment (CS). This study aims to elucidate the roles of these domains or segments in the metHb/IsdB reaction. Deletion of CS does not alter the kinetics and equilibrium of the reaction. Sequential deletions of NS and N1 in NS-N1-MD-N2 progressively reduce heme transfer rates and change the kinetic pattern from one to two phases, but have no effect on the equilibrium of the heme transfer reaction, whereas further deletion of MD reduces the percentage of transferred metHb heme. MD-N2 has higher affinity for heme than N2. MD in trans reduces rates of heme dissociation from holo-N2 and increases the percentage of metHb heme captured by N2 by 4.5 fold. NS-N1-MD and N2, but not NS-N1, MD, and N2, reconstitute the rapid metHb/IsdB reaction. NS-N1-MD-NIsdC, a fusion protein of NS-N1-MD and the NEAT domain of IsdC, slowly acquires heme from metHb by itself but together with N2 results in rapid heme loss from metHb. Thus, NS-N1 and MD domains specifically and critically contribute to the kinetics and equilibrium of the metHb/IsdB reaction, respectively. These findings support a mechanism of direct heme acquisition by IsdB in which MD enhances the affinity of N2 for heme to thermodynamically drive heme transfer from metHb to IsdB and in which NS is required for the rapid and single phase kinetics of the metHb/IsdB reaction.
Related Links	http://dx.doi.org/10.1371/journal.pone.0100744
Starting Page	100744
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	6
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-06-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Functionally distinct NEAT (NEAr Transporter) domains within the Staphylococcus aureus IsdH/HarA protein extract heme from methemoglobin.

Functionally Distinct NEAT (NEAr Transporter) Domains within the Staphylococcus aureus IsdH/HarA Protein Extract Heme from Methemoglobin

Structure–function analyses reveal key features in Staphylococcus aureus IsdB-associated unfolding of the heme-binding pocket of human hemoglobin

Investigating Hemoglobin Capture and Heme Acquisition by the Pathogen Staphylococcus aureus

Pathway for heme uptake from human methemoglobin by the iron-regulated surface determinants system of Staphylococcus aureus.

$^{1}$H, $^{13}$C, $^{15}$N backbone and side chain NMR resonance assignments of the N-terminal NEAr iron transporter domain 1 (NEAT 1) of the hemoglobin receptor IsdB of Staphylococcus aureus

Functionally Distinct NEAT (NEAr Transporter) Domains within the Staphylococcus aureus IsdH/HarA Protein Extract Heme from Methemoglobin*

Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography

The IsdC protein from Staphylococcus aureus uses a flexible binding pocket to capture heme.

Non-Heme-Binding Domains and Segments of the Staphylococcus aureus IsdB Protein Critically Contribute to the Kinetics and Equilibrium of Heme Acquisition from Methemoglobin

Similar Documents

Functionally distinct NEAT (NEAr Transporter) domains within the Staphylococcus aureus IsdH/HarA protein extract heme from methemoglobin.

Functionally Distinct NEAT (NEAr Transporter) Domains within the Staphylococcus aureus IsdH/HarA Protein Extract Heme from Methemoglobin

Structure–function analyses reveal key features in Staphylococcus aureus IsdB-associated unfolding of the heme-binding pocket of human hemoglobin

Investigating Hemoglobin Capture and Heme Acquisition by the Pathogen Staphylococcus aureus

Pathway for heme uptake from human methemoglobin by the iron-regulated surface determinants system of Staphylococcus aureus.

$^{1}$H, $^{13}$C, $^{15}$N backbone and side chain NMR resonance assignments of the N-terminal NEAr iron transporter domain 1 (NEAT 1) of the hemoglobin receptor IsdB of Staphylococcus aureus

Functionally Distinct NEAT (NEAr Transporter) Domains within the Staphylococcus aureus IsdH/HarA Protein Extract Heme from Methemoglobin*

Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography

The IsdC protein from Staphylococcus aureus uses a flexible binding pocket to capture heme.

Non-Heme-Binding Domains and Segments of the Staphylococcus aureus IsdB Protein Critically Contribute to the Kinetics and Equilibrium of Heme Acquisition from Methemoglobin