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| | <StructureSection load='6siu' size='340' side='right'caption='[[6siu]], [[Resolution|resolution]] 2.49Å' scene=''> | | <StructureSection load='6siu' size='340' side='right'caption='[[6siu]], [[Resolution|resolution]] 2.49Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6siu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hiss2 Hiss2] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SIU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SIU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6siu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Histophilus_somni_2336 Histophilus somni 2336] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SIU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LJN:[(2~{R},3~{S},4~{R},5~{R})-5-[4-(acetamidomethyl)-1,2,3-triazol-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>LJN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.49Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ibpA, p76, HSM_1489 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=228400 HISS2]), CDC42 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LJN:[(2~{R},3~{S},4~{R},5~{R})-5-[4-(acetamidomethyl)-1,2,3-triazol-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>LJN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Small_monomeric_GTPase Small monomeric GTPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.5.2 3.6.5.2] </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=6siu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6siu OCA], [https://pdbe.org/6siu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6siu RCSB], [https://www.ebi.ac.uk/pdbsum/6siu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6siu ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6siu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6siu OCA], [http://pdbe.org/6siu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6siu RCSB], [http://www.ebi.ac.uk/pdbsum/6siu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6siu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IBPA_HISS2 IBPA_HISS2]] Adenylyltransferase involved in virulence by mediating the addition of adenosine 5'-monophosphate (AMP) to specific tyrosine residue of host Rho GTPases RhoA, Rac and Cdc42. The resulting AMPylation inactivates Rho GTPases, thereby inhibiting actin assembly in infected cells. Probably also acts as a cysteine protease, which may play a central role after invasion of host cell and in virulence. Possible member (with IbpB) of a 2 partner secretion. Probably able to bind bovine epithelial cells (host cells). May participate in the formation of fibrils at the surface of the bacteria.<ref>PMID:12631474</ref> <ref>PMID:19362538</ref> <ref>PMID:20622875</ref> <ref>PMID:9317034</ref> [[http://www.uniprot.org/uniprot/CDC42_HUMAN CDC42_HUMAN]] Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration.<ref>PMID:14978216</ref> <ref>PMID:15642749</ref> <ref>PMID:17038317</ref> | + | [https://www.uniprot.org/uniprot/IBPA_HISS2 IBPA_HISS2] Adenylyltransferase involved in virulence by mediating the addition of adenosine 5'-monophosphate (AMP) to specific tyrosine residue of host Rho GTPases RhoA, Rac and Cdc42. The resulting AMPylation inactivates Rho GTPases, thereby inhibiting actin assembly in infected cells. Probably also acts as a cysteine protease, which may play a central role after invasion of host cell and in virulence. Possible member (with IbpB) of a 2 partner secretion. Probably able to bind bovine epithelial cells (host cells). May participate in the formation of fibrils at the surface of the bacteria.<ref>PMID:12631474</ref> <ref>PMID:19362538</ref> <ref>PMID:20622875</ref> <ref>PMID:9317034</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6siu" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6siu" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hiss2]] | + | [[Category: Histophilus somni 2336]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Small monomeric GTPase]]
| + | [[Category: Albers M]] |
| - | [[Category: Albers, M]] | + | [[Category: Gulen B]] |
| - | [[Category: Gulen, B]] | + | [[Category: Hedberg C]] |
| - | [[Category: Hedberg, C]] | + | [[Category: Itzen A]] |
| - | [[Category: Itzen, A]] | + | [[Category: Pogenberg V]] |
| - | [[Category: Pogenberg, V]] | + | [[Category: Roselin M]] |
| - | [[Category: Roselin, M]] | + | |
| - | [[Category: Adenosine monophosphate-protein transferase]]
| + | |
| - | [[Category: Fic domain]]
| + | |
| - | [[Category: Proximity enabled coupling]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
IBPA_HISS2 Adenylyltransferase involved in virulence by mediating the addition of adenosine 5'-monophosphate (AMP) to specific tyrosine residue of host Rho GTPases RhoA, Rac and Cdc42. The resulting AMPylation inactivates Rho GTPases, thereby inhibiting actin assembly in infected cells. Probably also acts as a cysteine protease, which may play a central role after invasion of host cell and in virulence. Possible member (with IbpB) of a 2 partner secretion. Probably able to bind bovine epithelial cells (host cells). May participate in the formation of fibrils at the surface of the bacteria.[1] [2] [3] [4]
Publication Abstract from PubMed
Various pathogenic bacteria use post-translational modifications to manipulate the central components of host cell functions. Many of the enzymes released by these bacteria belong to the large Fic family, which modify targets with nucleotide monophosphates. The lack of a generic method for identifying the cellular targets of Fic family enzymes hinders investigation of their role and the effect of the post-translational modification. Here, we establish an approach that uses reactive co-substrate-linked enzymes for proteome profiling. We combine synthetic thiol-reactive nucleotide derivatives with recombinantly produced Fic enzymes containing strategically placed cysteines in their active sites to yield reactive binary probes for covalent substrate capture. The binary complexes capture their targets from cell lysates and permit subsequent identification. Furthermore, we determined the structures of low-affinity ternary enzyme-nucleotide-substrate complexes by applying a covalent-linking strategy. This approach thus allows target identification of the Fic enzymes from both bacteria and eukarya.
Identification of targets of AMPylating Fic enzymes by co-substrate-mediated covalent capture.,Gulen B, Rosselin M, Fauser J, Albers MF, Pett C, Krisp C, Pogenberg V, Schluter H, Hedberg C, Itzen A Nat Chem. 2020 Aug;12(8):732-739. doi: 10.1038/s41557-020-0484-6. Epub 2020 Jul, 6. PMID:32632184[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sanders JD, Bastida-Corcuera FD, Arnold KF, Wunderlich AC, Corbeil LB. Genetic manipulation of immunoglobulin binding proteins of Haemophilus somnus. Microb Pathog. 2003 Mar;34(3):131-9. PMID:12631474
- ↑ Worby CA, Mattoo S, Kruger RP, Corbeil LB, Koller A, Mendez JC, Zekarias B, Lazar C, Dixon JE. The fic domain: regulation of cell signaling by adenylylation. Mol Cell. 2009 Apr 10;34(1):93-103. doi: 10.1016/j.molcel.2009.03.008. PMID:19362538 doi:http://dx.doi.org/10.1016/j.molcel.2009.03.008
- ↑ Xiao J, Worby CA, Mattoo S, Sankaran B, Dixon JE. Structural basis of Fic-mediated adenylylation. Nat Struct Mol Biol. 2010 Aug;17(8):1004-10. Epub 2010 Jul 11. PMID:20622875 doi:10.1038/nsmb.1867
- ↑ Corbeil LB, Bastida-Corcuera FD, Beveridge TJ. Haemophilus somnus immunoglobulin binding proteins and surface fibrils. Infect Immun. 1997 Oct;65(10):4250-7. PMID:9317034
- ↑ Gulen B, Rosselin M, Fauser J, Albers MF, Pett C, Krisp C, Pogenberg V, Schluter H, Hedberg C, Itzen A. Identification of targets of AMPylating Fic enzymes by co-substrate-mediated covalent capture. Nat Chem. 2020 Aug;12(8):732-739. doi: 10.1038/s41557-020-0484-6. Epub 2020 Jul, 6. PMID:32632184 doi:http://dx.doi.org/10.1038/s41557-020-0484-6
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