PMID- 28642848
OWN - NLM
STAT- MEDLINE
DCOM- 20180223
LR  - 20181113
IS  - 2235-2988 (Electronic)
IS  - 2235-2988 (Linking)
VI  - 7
DP  - 2017
TI  - Mycobacterium tuberculosis Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) 
      Functions as a Receptor for Human Lactoferrin.
PG  - 245
LID - 10.3389/fcimb.2017.00245 [doi]
LID - 245
AB  - Iron is crucial for the survival of living cells, particularly the human pathogen 
      Mycobacterium tuberculosis (M.tb) which uses multiple strategies to acquire and 
      store iron. M.tb synthesizes high affinity iron chelators (siderophores), these 
      extract iron from host iron carrier proteins such as transferrin (Tf) and 
      lactoferrin (Lf). Recent studies have revealed that M.tb may also relocate 
      several housekeeping proteins to the cell surface for capture and internalization 
      of host iron carrier protein transferrin. One of the identified receptors is the 
      glycolytic enzyme Glyceraldehyde-3-phosphate dehydrogenase (GAPDH). This 
      conserved multifunctional protein has been identified as a virulence factor in 
      several other bacterial species. Considering the close structural and functional 
      homology between the two major human iron carrier proteins (Tf and Lf) and the 
      fact that Lf is abundantly present in lung fluid (unlike Tf which is present in 
      plasma), we evaluated whether GAPDH also functions as a dual receptor for Lf. The 
      current study demonstrates that human Lf is sequestered at the bacterial surface 
      by GAPDH. The affinity of Lf-GAPDH (31.7 +/- 1.68 nM) is higher as compared to 
      Tf-GAPDH (160 +/- 24 nM). Two GAPDH mutants were analyzed for their enzymatic 
      activity and interaction with Lf. Lastly, the present computational studies offer 
      the first significant insights for the 3D structure of monomers and assembled 
      tetramer with the associated co-factor NAD(+). Sequence analysis and structural 
      modeling identified the surface exposed, evolutionarily conserved and functional 
      residues and predicted the effect of mutagenesis on GAPDH.
FAU - Malhotra, Himanshu
AU  - Malhotra H
AD  - Cell Biology and Immunology, Council of Scientific and Industrial 
      Research-Institute of Microbial TechnologyChandigarh, India.
FAU - Patidar, Anil
AU  - Patidar A
AD  - Cell Biology and Immunology, Council of Scientific and Industrial 
      Research-Institute of Microbial TechnologyChandigarh, India.
FAU - Boradia, Vishant M
AU  - Boradia VM
AD  - Department of Biotechnology, National Institute of Pharmaceutical Education and 
      ResearchPunjab, India.
FAU - Kumar, Rajender
AU  - Kumar R
AD  - Department of Pharmacoinformatics, National Institute of Pharmaceutical Education 
      and ResearchPunjab, India.
FAU - Nimbalkar, Rakesh D
AU  - Nimbalkar RD
AD  - Department of Pharmacoinformatics, National Institute of Pharmaceutical Education 
      and ResearchPunjab, India.
FAU - Kumar, Ajay
AU  - Kumar A
AD  - Department of Biotechnology, National Institute of Pharmaceutical Education and 
      ResearchPunjab, India.
FAU - Gani, Zahid
AU  - Gani Z
AD  - Department of Biotechnology, National Institute of Pharmaceutical Education and 
      ResearchPunjab, India.
FAU - Kaur, Rajbeer
AU  - Kaur R
AD  - Department of Biotechnology, National Institute of Pharmaceutical Education and 
      ResearchPunjab, India.
FAU - Garg, Prabha
AU  - Garg P
AD  - Department of Pharmacoinformatics, National Institute of Pharmaceutical Education 
      and ResearchPunjab, India.
FAU - Raje, Manoj
AU  - Raje M
AD  - Cell Biology and Immunology, Council of Scientific and Industrial 
      Research-Institute of Microbial TechnologyChandigarh, India.
FAU - Raje, Chaaya I
AU  - Raje CI
AD  - Department of Biotechnology, National Institute of Pharmaceutical Education and 
      ResearchPunjab, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170608
PL  - Switzerland
TA  - Front Cell Infect Microbiol
JT  - Frontiers in cellular and infection microbiology
JID - 101585359
RN  - 0 (LTF protein, human)
RN  - 0 (Transferrin)
RN  - 0 (Virulence Factors)
RN  - E1UOL152H7 (Iron)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - EC 3.4.21.- (Lactoferrin)
SB  - IM
MH  - Binding Sites
MH  - Cell Line
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/chemistry/genetics/*metabolism
MH  - Humans
MH  - Iron/metabolism
MH  - Lactoferrin/*metabolism
MH  - Lung
MH  - Models, Molecular
MH  - Mutation
MH  - Mycobacterium tuberculosis/cytology/*enzymology/*metabolism
MH  - Protein Conformation
MH  - Sequence Analysis
MH  - THP-1 Cells
MH  - Transferrin/metabolism
MH  - Virulence Factors
PMC - PMC5462994
OTO - NOTNLM
OT  - Mycobacterium tuberculosis
OT  - glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
OT  - iron
OT  - lactoferrin
OT  - transferrin
EDAT- 2017/06/24 06:00
MHDA- 2018/02/24 06:00
PMCR- 2017/01/01
CRDT- 2017/06/24 06:00
PHST- 2017/03/21 00:00 [received]
PHST- 2017/05/26 00:00 [accepted]
PHST- 2017/06/24 06:00 [entrez]
PHST- 2017/06/24 06:00 [pubmed]
PHST- 2018/02/24 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fcimb.2017.00245 [doi]
PST - epublish
SO  - Front Cell Infect Microbiol. 2017 Jun 8;7:245. doi: 10.3389/fcimb.2017.00245. 
      eCollection 2017.