Mycobacterium tuberculosis ArfA Rv0899
From Proteopedia
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<StructureSection load='2l26' size='350' side='right' caption='NMR structure of uncharacterized protein Rv0899 (PDB code [[2l26]])' scene='61/612805/N-c_rainbow/1'> | <StructureSection load='2l26' size='350' side='right' caption='NMR structure of uncharacterized protein Rv0899 (PDB code [[2l26]])' scene='61/612805/N-c_rainbow/1'> | ||
| - | == | + | ==Background=== |
| - | The Rv0899 ArfA protein belongs to the OmpA (outer membrane protein A) family of outer membrane proteins and has been proposed to act as an outer membrane [[porin]] with ion channel activity and contributes to the bacterium's adaptation to the acidic environment in phagosome [http://en.wikipedia.org/wiki/Phagosome]during infection <ref>PMID: 21117233 </ref>. | + | The Rv0899 ArfA protein belongs to the OmpA (outer membrane protein A) family of outer membrane proteins and has been proposed to act as an outer membrane [[porin]] with ion channel activity and contributes to the bacterium's adaptation to the acidic environment in phagosome [http://en.wikipedia.org/wiki/Phagosome]during infection <ref>PMID: 21117233 </ref>. Rv0899 protein encoded by an ammonia release facilator operon that is necessary for rapid ammonia secretion, pH neutralization and adaptation to acidic environments in vitro. Two M. tuberculosis H37Rv genes (Rv0900 [[http://www.uniprot.org/uniprot/P9WJG7 ARFB_MYCTU]] and Rv0901 [[http://www.uniprot.org/uniprot/P9WJG5 ARFC_MYCTU]] ) adjacent to Rv0899 also encode putative membrane proteins, and are found exclusively in association with Rv0899 in the same pathogenic mycobacteria, suggesting that the three may constitute an operon dedicated to a common function. |
| + | Asparagine is the primary ammonia source for Mycobacterium tuberculosis H37Rv at acidic pH <ref>PMID: 21410778 </ref>. | ||
The deletion of this gene impairs the uptake of some water-soluble substances, such as serine, glucose, and glycerol <ref>PMID: 12366842 </ref>. | The deletion of this gene impairs the uptake of some water-soluble substances, such as serine, glucose, and glycerol <ref>PMID: 12366842 </ref>. | ||
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<ref>PMID: 22108166 </ref> | <ref>PMID: 22108166 </ref> | ||
| - | 2. Bacterium's adaptation to the acidic environment of the phagosome during infection. | + | 2. Bacterium's adaptation to the acidic environment of the phagosome during infection. |
| - | + | The amino acid pair <scene name='61/612805/Asn111_and_gly112/1'> Asn111-Gly112 </scene>, located at the end of α1 and preceding L3, undergoes in-vitro deamidation, a pH-dependent reaction whereby Asn is converted to Asp and ammonia is released. Asparagine residues preceding glycine, and situated in conformationally flexible regions of proteins, are frequently deamidated, with potentially significant consequences for protein regulation and function. In the case of Rv0899, deamidation and the concomitant release of ammonia could have important consequences for the acid adaptation function of the protein. <ref>PMID: 20199110</ref> | |
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| - | It exhibits pH-dependent conformational dynamics 232, 225, 240, 244, 281, 285 <scene name='61/612805/D236_before_mutation/1'>in neutral pH (D236) </scene> and a more ordered structure at <scene name='61/612805/D236a_after_mut/3'>acidic pH (D236A) </scene>, which could be related to its acid stress response. | ||
[[Image:Asparaginase-reaction.jpg|250px]] | [[Image:Asparaginase-reaction.jpg|250px]] | ||
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| + | It exhibits pH-dependent conformational dynamics 232, 225, 240, 244, 281, 285 <scene name='61/612805/D236_before_mutation/1'>in neutral pH (D236) </scene> and a more ordered structure at <scene name='61/612805/D236a_after_mut/3'>acidic pH (D236A) </scene>, which could be related to its acid stress response. | ||
Its functions in acid stress protection and [peptidoglycan][http://en.wikipedia.org/wiki/Peptidoglycan] binding site <scene name='61/612805/Peptidoglycan_binding_site/1'>(R277, R319, T261, D262, N270)</scene> suggest a link between the acid stress response and the physicochemical properties of the mycobacterial cell wall. These residues are strictly conserved in the OmpA -like family <ref>PMID: 22206986 </ref>. | Its functions in acid stress protection and [peptidoglycan][http://en.wikipedia.org/wiki/Peptidoglycan] binding site <scene name='61/612805/Peptidoglycan_binding_site/1'>(R277, R319, T261, D262, N270)</scene> suggest a link between the acid stress response and the physicochemical properties of the mycobacterial cell wall. These residues are strictly conserved in the OmpA -like family <ref>PMID: 22206986 </ref>. | ||
Revision as of 19:45, 23 January 2015
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