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| | <StructureSection load='3oxh' size='340' side='right'caption='[[3oxh]], [[Resolution|resolution]] 1.75Å' scene=''> | | <StructureSection load='3oxh' size='340' side='right'caption='[[3oxh]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3oxh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OXH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3oxh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OXH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PMB:PARA-MERCURY-BENZENESULFONIC+ACID'>PMB</scene>, <scene name='pdbligand=XYL:D-XYLITOL'>XYL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cfp30B, MT0606, MTV039.15, Rv0577, TB27.3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PMB:PARA-MERCURY-BENZENESULFONIC+ACID'>PMB</scene>, <scene name='pdbligand=XYL:D-XYLITOL'>XYL</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3oxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oxh OCA], [https://pdbe.org/3oxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oxh RCSB], [https://www.ebi.ac.uk/pdbsum/3oxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oxh ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3oxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oxh OCA], [https://pdbe.org/3oxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oxh RCSB], [https://www.ebi.ac.uk/pdbsum/3oxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oxh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/CFP32_MYCTU CFP32_MYCTU] May function as a glyoxylase involved in the methylglyoxal detoxification pathway (PubMed:20975714). Induces maturation of dendritic cells in a TLR2-dependent manner, causing increased expression of cell-surface molecules (CD80, CD86, MHC class I and II) and pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1 beta and IL-12p70). Acts via both the NF-kappa-B and MAPK signaling pathways. Induces Th1-polarized immune responses (PubMed:22415304).<ref>PMID:20975714</ref> <ref>PMID:22415304</ref> |
| - | Mycobacterium tuberculosis protein Rv0577 is a prominent antigen in tuberculosis patients, the component responsible for neutral red staining of virulent strains of M. tuberculosis, a putative component in a methylglyoxal detoxification pathway, and an agonist of toll-like receptor 2. It also has an amino acid sequence that is 36% identical to that of Streptomyces coelicolor AfsK-binding protein A (KbpA), a component in the complex secondary metabolite pathways in the Streptomyces genus. To gain insight into the biological function of Rv0577 and the family of KpbA kinase regulators, the crystal structure for Rv0577 was determined to a resolution of 1.75 A, binding properties with neutral red and deoxyadenosine were surveyed, backbone dynamics were measured, and thermal stability was assayed by circular dichroism spectroscopy. The protein is composed of four approximate repeats with a betaalphabetabetabeta topology arranged radially in consecutive pairs to form two continuous eight-strand beta-sheets capped on both ends with an alpha-helix. The two beta-sheets intersect in the center at roughly a right angle and form two asymmetric deep "saddles" that may serve to bind ligands. Nuclear magnetic resonance chemical shift perturbation experiments show that neutral red and deoxyadenosine bind to Rv0577. Binding to deoxyadenosine is weaker with an estimated dissociation constants of 4.1 +/- 0.3 mM for saddle 1. Heteronuclear steady-state {1H}-15N nuclear Overhauser effect, T1, and T2 values were generally uniform throughout the sequence with only a few modest pockets of differences. Circular dichroism spectroscopy characterization of the thermal stability of Rv0577 indicated irreversible unfolding upon heating with an estimated melting temperature of 56 degrees C.
| + | |
| - | | + | |
| - | Structural and Biophysical Characterization of the Mycobacterium tuberculosis Protein Rv0577, a Protein Associated with Neutral Red Staining of Virulent Tuberculosis Strains and Homologue of the Streptomyces coelicolor Protein KbpA.,Buchko GW, Echols N, Flynn EM, Ng HL, Stephenson S, Kim HB, Myler PJ, Terwilliger TC, Alber T, Kim CY Biochemistry. 2017 Aug 1;56(30):4015-4027. doi: 10.1021/acs.biochem.7b00511. Epub, 2017 Jul 25. PMID:28692281<ref>PMID:28692281</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3oxh" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Alber, T]] | |
| - | [[Category: Echols, N]] | |
| - | [[Category: Flynn, E M]] | |
| - | [[Category: Ng, H L]] | |
| - | [[Category: Stephenson, S]] | |
| - | [[Category: Structural genomic]] | |
| - | [[Category: Antibiotic resistance]] | |
| - | [[Category: Babbb fold]] | |
| - | [[Category: Hydrolase inhibitor]] | |
| - | [[Category: Kinase regulation]] | |
| | [[Category: Mycobacterium tuberculosis]] | | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: PSI, Protein structure initiative]] | + | [[Category: Alber T]] |
| - | [[Category: Tbsgc]] | + | [[Category: Echols N]] |
| | + | [[Category: Flynn EM]] |
| | + | [[Category: Ng H-L]] |
| | + | [[Category: Stephenson S]] |
| Structural highlights
Function
CFP32_MYCTU May function as a glyoxylase involved in the methylglyoxal detoxification pathway (PubMed:20975714). Induces maturation of dendritic cells in a TLR2-dependent manner, causing increased expression of cell-surface molecules (CD80, CD86, MHC class I and II) and pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1 beta and IL-12p70). Acts via both the NF-kappa-B and MAPK signaling pathways. Induces Th1-polarized immune responses (PubMed:22415304).[1] [2]
References
- ↑ Pethe K, Sequeira PC, Agarwalla S, Rhee K, Kuhen K, Phong WY, Patel V, Beer D, Walker JR, Duraiswamy J, Jiricek J, Keller TH, Chatterjee A, Tan MP, Ujjini M, Rao SP, Camacho L, Bifani P, Mak PA, Ma I, Barnes SW, Chen Z, Plouffe D, Thayalan P, Ng SH, Au M, Lee BH, Tan BH, Ravindran S, Nanjundappa M, Lin X, Goh A, Lakshminarayana SB, Shoen C, Cynamon M, Kreiswirth B, Dartois V, Peters EC, Glynne R, Brenner S, Dick T. A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy. Nat Commun. 2010 Aug 24;1(5):57. PMID:20975714 doi:10.1038/ncomms1060
- ↑ Byun EH, Kim WS, Kim JS, Jung ID, Park YM, Kim HJ, Cho SN, Shin SJ. Mycobacterium tuberculosis Rv0577, a novel TLR2 agonist, induces maturation of dendritic cells and drives Th1 immune response. FASEB J. 2012 Jun;26(6):2695-711. PMID:22415304 doi:10.1096/fj.11-199588
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