Mycobacterium tuberculosis ArfA Rv0899: Difference between revisions
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The C domain <scene name='61/612805/Secondary_structure_c/1'>residues 201-326</scene> The C domain of wild-type ArfA <scene name='61/612805/C_domain/3'></scene> <scene name='61/612805/C_domain_1/1'> folds </scene> into four {{Template:ColorKey_Strand}} and four {{Template:ColorKey_Helix}}.Three parallel (β1, β2, β3) and one antiparallel (β4) β-strands form a four-stranded β-sheet (β1–β4-β2–β3) that packs against three α-helices (α1, α2, α3), while a fourth helix (α4) extends from the N-terminus of β4. The structure <scene name='61/612805/C_domain_stabilization/2'> is stabilized </scene> by disulfide bond between C208 and C250, by a network of hydrophobic contacts between α1, α2 and β4 (L211, I215, V243, L247, Ile323 and V325) between side chains and by a hydrogen bond between the backbone amide of V325 and the side-chain carbonyl of Q212. | The C domain <scene name='61/612805/Secondary_structure_c/1'>residues 201-326</scene> The C domain of wild-type ArfA <scene name='61/612805/C_domain/3'></scene> <scene name='61/612805/C_domain_1/1'> folds </scene> into four {{Template:ColorKey_Strand}} and four {{Template:ColorKey_Helix}}.Three parallel (β1, β2, β3) and one antiparallel (β4) β-strands form a four-stranded β-sheet (β1–β4-β2–β3) that packs against three α-helices (α1, α2, α3), while a fourth helix (α4) extends from the N-terminus of β4. The structure <scene name='61/612805/C_domain_stabilization/2'> is stabilized </scene> by disulfide bond between C208 and C250, by a network of hydrophobic contacts between α1, α2 and β4 (L211, I215, V243, L247, Ile323 and V325) between side chains and by a hydrogen bond between the backbone amide of V325 and the side-chain carbonyl of Q212. | ||
==Function== | ==Function== | ||
Stress response of the bacterium and adaptation to the acidic external environment. | Stress response of the bacterium and adaptation to the acidic external environment. | ||
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3. Stabilization of the outer membrane: | 3. Stabilization of the outer membrane: | ||
1. pH-dependent conformational dynamics of hydrophobic cluster of L232, F225, L240, A244, V281, L285 <scene name='61/612805/D236_before_mutation/1'>in neutral pH (D236) </scene> that folds to a more ordered structure like a flap at <scene name='61/612805/D236a_after_mut/3'>acidic pH (D236A) </scene>. | 1. pH-dependent conformational dynamics of hydrophobic cluster of L232, F225, L240, A244, V281, L285 <scene name='61/612805/D236_before_mutation/1'>in neutral pH (D236) </scene> that folds to a more ordered structure like a flap at <scene name='61/612805/D236a_after_mut/3'>acidic pH (D236A) </scene>. | ||
2. | |||
The B domain has homology with conserved putative <scene name='61/612805/Conserved_g95_and_g164_in_bon/2'>lipid-binding BON</scene> (bacterial OsmY and nodulation) superfamily domains and conserved Gly95 and Gly164 [http://www.ebi.ac.uk/interpro/entry/IPR014004], which putative | |||
The C domain has homology to the OmpA-C-like superfamily of periplasmic peptidoglycan-binding sequences, found in several types of bacterial membrane proteins.Contribution for structural strength to the bacterial cell wall under acid or other stress conditionsIts functions by binding to peptidoglycan biosyntheesis intermediate uridine-5-'-diphosphate-MurNAc–L-Ala–D-γ-Glu–m-DAP–D-Ala–D-Ala (UMDP) [http://en.wikipedia.org/wiki/Peptidoglycan] binding site. <scene name='61/612805/Peptidoglycan_binding_site/1'>(R277, R319, T261, D262, N270)</scene>. These residues are strictly conserved in the OmpA -like family The side chain of m-DAP is stabilized by charge-charge interactions between its electronegative carbonyl group with R277 and R319 guanidinium groups and with the N270 carboxamide and between its electropositive amino group with the D262 carboxyl and the T261 hydroxyl. UMDP could interact through contacts of its γ-Glu3 and Ala2 backbone amides with the side-chain hydroxyl of S266, of its MurNAc O3 with the amide proton of E267, and of its MurNAc NH2 with the E267 carboxyl <ref>PMID: 22206986 </ref>. | 2. Binding to peptidoglycan and phospholipid layer. | ||
a) The B domain has homology with conserved putative <scene name='61/612805/Conserved_g95_and_g164_in_bon/2'>lipid-binding BON</scene> (bacterial OsmY and nodulation) superfamily domains and conserved Gly95 and Gly164 [http://www.ebi.ac.uk/interpro/entry/IPR014004], which putative functions are prevention of shrinkage of inner and outer membrane by binding to the phospholipid layer, nitrogen fixation and / or nitrogen metabolism <ref>PMID: 12878000 </ref>. | |||
b)The C domain has homology to the OmpA-C-like superfamily of periplasmic peptidoglycan-binding sequences, found in several types of bacterial membrane proteins.Contribution for structural strength to the bacterial cell wall under acid or other stress conditionsIts functions by binding to peptidoglycan biosyntheesis intermediate uridine-5-'-diphosphate-MurNAc–L-Ala–D-γ-Glu–m-DAP–D-Ala–D-Ala (UMDP) [http://en.wikipedia.org/wiki/Peptidoglycan] binding site. <scene name='61/612805/Peptidoglycan_binding_site/1'>(R277, R319, T261, D262, N270)</scene>. These residues are strictly conserved in the OmpA -like family. The side chain of m-DAP is stabilized by charge-charge interactions between its electronegative carbonyl group with R277 and R319 guanidinium groups and with the N270 carboxamide and between its electropositive amino group with the D262 carboxyl and the T261 hydroxyl. UMDP could interact through contacts of its γ-Glu3 and Ala2 backbone amides with the side-chain hydroxyl of S266, of its MurNAc O3 with the amide proton of E267, and of its MurNAc NH2 with the E267 carboxyl <ref>PMID: 22206986 </ref>. | |||
[[Image:123456.jpg|250px]] [[Image:MurNac11.jpg|250px]] | [[Image:123456.jpg|250px]] [[Image:MurNac11.jpg|250px]] | ||