|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal Structure of Mtb-ribA2 (Rv1415)== | | ==Crystal Structure of Mtb-ribA2 (Rv1415)== |
| - | <StructureSection load='4i14' size='340' side='right' caption='[[4i14]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='4i14' size='340' side='right'caption='[[4i14]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4i14]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycta Mycta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I14 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I14 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4i14]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Ra Mycobacterium tuberculosis H37Ra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I14 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mio|3mio]]</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=4i14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i14 OCA], [https://pdbe.org/4i14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i14 RCSB], [https://www.ebi.ac.uk/pdbsum/4i14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i14 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MRA_1424, ribBA, Rv1415 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=419947 MYCTA])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4i14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i14 OCA], [http://pdbe.org/4i14 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i14 RCSB], [http://www.ebi.ac.uk/pdbsum/4i14 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i14 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RIBBA_MYCTA RIBBA_MYCTA]] Catalyzes the conversion of D-ribulose 5-phosphate to formate and 3,4-dihydroxy-2-butanone 4-phosphate (By similarity). Catalyzes the conversion of GTP to 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (DARP), formate and pyrophosphate (By similarity). | + | [https://www.uniprot.org/uniprot/RIBBA_MYCTA RIBBA_MYCTA] Catalyzes the conversion of D-ribulose 5-phosphate to formate and 3,4-dihydroxy-2-butanone 4-phosphate (By similarity). Catalyzes the conversion of GTP to 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (DARP), formate and pyrophosphate (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Mycta]] | + | [[Category: Large Structures]] |
| - | [[Category: Gautam, R]] | + | [[Category: Mycobacterium tuberculosis H37Ra]] |
| - | [[Category: Karthikeyan, S]] | + | [[Category: Gautam R]] |
| - | [[Category: Kumar, P]] | + | [[Category: Karthikeyan S]] |
| - | [[Category: Sharma, N]] | + | [[Category: Kumar P]] |
| - | [[Category: Singh, M]] | + | [[Category: Sharma N]] |
| - | [[Category: Yadav, S]] | + | [[Category: Singh M]] |
| - | [[Category: Antimicrobial]]
| + | [[Category: Yadav S]] |
| - | [[Category: Dhbp]]
| + | |
| - | [[Category: Gchii]]
| + | |
| - | [[Category: Gtp]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Riba2]]
| + | |
| - | [[Category: Riboflavin]]
| + | |
| Structural highlights
Function
RIBBA_MYCTA Catalyzes the conversion of D-ribulose 5-phosphate to formate and 3,4-dihydroxy-2-butanone 4-phosphate (By similarity). Catalyzes the conversion of GTP to 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (DARP), formate and pyrophosphate (By similarity).
Publication Abstract from PubMed
The enzymes 3,4-dihydroxy-2-butanone 4-phosphate synthase (DHBPS) and GTP cyclohydrolase II (GCHII) catalyze the initial steps of both branches of the bacterial riboflavin-biosynthesis pathway. The structures and molecular mechanisms of DHBPS and GCHII as separate polypeptides are known; however, their organization and molecular mechanism as a bifunctional enzyme are unknown to date. Here, the crystal structure of an essential bifunctional DHBPS/GCHII enzyme from Mycobacterium tuberculosis (Mtb-ribA2) is reported at 3.0 A resolution. The crystal structure revealed two conformationally different molecules of Mtb-ribA2 in the asymmetric unit that form a dimer via their GCHII domains. Interestingly, analysis of the crystal packing revealed a long `helical-like oligomer' formed by DHBPS and GCHII functional homodimers, thus generating an `open-ended' unit-cell lattice. However, size-exclusion chromatography studies suggest that Mtb-ribA2 exists as a dimer in solution. To understand the discrepancy between the oligomerization observed in solution and in the crystal structure, the DHBPS (Mtb-DHBPS) and GCHII (Mtb-GCHII) domains of Mtb-ribA2 have been cloned, expressed and purified as His-tagged proteins. Size-exclusion chromatography studies indicated that Mtb-GCHII is a dimer while Mtb-DHBPS exists as a monomer in solution. Moreover, kinetic studies revealed that the GCHII activities of Mtb-ribA2 and Mtb-GCHII are similar, while the DHBPS activity of Mtb-ribA2 is much higher than that of Mtb-DHBPS alone. Taken together, the results strongly suggest that Mtb-ribA2 exists as a dimer formed through its GCHII domains and requires full-length Mtb-ribA2 for optimal DHBPS activity.
The crystal structure reveals the molecular mechanism of bifunctional 3,4-dihydroxy-2-butanone 4-phosphate synthase/GTP cyclohydrolase II (Rv1415) from Mycobacterium tuberculosis.,Singh M, Kumar P, Yadav S, Gautam R, Sharma N, Karthikeyan S Acta Crystallogr D Biol Crystallogr. 2013 Sep;69(Pt 9):1633-44. doi:, 10.1107/S0907444913011402. Epub 2013 Aug 15. PMID:23999287[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Singh M, Kumar P, Yadav S, Gautam R, Sharma N, Karthikeyan S. The crystal structure reveals the molecular mechanism of bifunctional 3,4-dihydroxy-2-butanone 4-phosphate synthase/GTP cyclohydrolase II (Rv1415) from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr. 2013 Sep;69(Pt 9):1633-44. doi:, 10.1107/S0907444913011402. Epub 2013 Aug 15. PMID:23999287 doi:http://dx.doi.org/10.1107/S0907444913011402
|
