|
|
| (15 intermediate revisions by the same user not shown) |
| Line 1: |
Line 1: |
| [[Image:2riz.jpg|left|200px]]<br /><applet load="2riz" size="350" color="white" frame="true" align="right" spinBox="true"
| |
| caption="2riz, resolution 1.450Å" />
| |
| '''Unliganded B-specific-1,3-galactosyltransferase G176R mutant (ABBB)'''<br />
| |
|
| |
|
| ==Overview== | | ==Unliganded B-specific-1,3-galactosyltransferase G176R mutant (ABBB)== |
| The final step in the enzymatic synthesis of the ABO(H) blood group A and, B antigens is catalyzed by two closely related glycosyltransferases, an, a-(1-3)-N-acetylgalactosaminyltransferase (GTA) and an, a-(1-3)-galactosyltransferase (GTB). Of their 354 amino acid residues, GTA, and GTB differ by only four 'critical' residues. High-resolution, structures for GTB and the GTA/GTB chimeric enzymes GTB/G176R and, GTB/G176R/G235S bound to a panel of donor and acceptor analog substrates, reveal 'open', 'semi-closed' and 'closed' conformations as the enzymes go, from the unliganded to the liganded states. In the 'open' form the, internal polypeptide loop (amino acid residues 177-195) adjacent to the, active site in the unliganded or H-antigen-bound enzymes is composed of, two a-helices spanning Arg180-Met186 and Arg188-Asp194 respectively. The, 'semi-closed' and closed forms of the enzymes are generated by binding of, UDP or of UDP and H-antigen analogs respectively, and show that these, helices merge to form a single distorted helical structure with, alternating a-310-a character that partially occludes the active site. The, 'closed' form is distinguished from the 'semi-closed' form by the ordering, of the final nine C-terminal residues through the formation of hydrogen, bonds to both UDP and H-antigen analogs. The 'semi-closed' forms for, various mutants generally show significantly more disorder than the 'open', forms, while the 'closed' forms display little or no disorder depending, strongly on the identity of residue 176. Finally, the use of synthetic, analogs reveals how H-antigen acceptor binding can be critical in, stabilizing the 'closed' conformation. These structures demonstrate a, delicately-balanced substrate recognition mechanism and give insight on, critical aspects of donor and acceptor specificity, on the order of, substrate binding, and on the requirements for catalysis.
| | <StructureSection load='2riz' size='340' side='right'caption='[[2riz]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | == Structural highlights == |
| | <table><tr><td colspan='2'>[[2riz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RIZ FirstGlance]. <br> |
| | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.45Å</td></tr> |
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=2riz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2riz OCA], [https://pdbe.org/2riz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2riz RCSB], [https://www.ebi.ac.uk/pdbsum/2riz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2riz ProSAT]</span></td></tr> |
| | </table> |
| | == Function == |
| | [https://www.uniprot.org/uniprot/BGAT_HUMAN BGAT_HUMAN] This protein is the basis of the ABO blood group system. The histo-blood group ABO involves three carbohydrate antigens: A, B, and H. A, B, and AB individuals express a glycosyltransferase activity that converts the H antigen to the A antigen (by addition of UDP-GalNAc) or to the B antigen (by addition of UDP-Gal), whereas O individuals lack such activity. |
| | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> |
| | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ri/2riz_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> |
| | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2riz ConSurf]. |
| | <div style="clear:both"></div> |
|
| |
|
| ==About this Structure== | | ==See Also== |
| 2RIZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Fucosylgalactoside_3-alpha-galactosyltransferase Fucosylgalactoside 3-alpha-galactosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.37 2.4.1.37] Known structural/functional Site: <scene name='pdbsite=AC1:Gol+Binding+Site+For+Residue+A+1'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RIZ OCA].
| | *[[Glycosyltransferase 3D structures|Glycosyltransferase 3D structures]] |
| | | __TOC__ |
| ==Reference==
| | </StructureSection> |
| ABO(H) blood group A and B glycosyltransferases recognize substrate via specific conformational changes., Alfaro JA, Zheng RB, Persson M, Letts JA, Polakowski R, Bai Y, Borisova SN, Seto NO, Lowary TL, Palcic MM, Evans SV, J Biol Chem. 2008 Jan 11;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18192272 18192272]
| |
| [[Category: Fucosylgalactoside 3-alpha-galactosyltransferase]]
| |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Single protein]] | | [[Category: Large Structures]] |
| [[Category: Alfaro, J.A.]] | | [[Category: Alfaro JA]] |
| [[Category: Evans, S.V.]] | | [[Category: Evans SV]] |
| [[Category: GOL]]
| |
| [[Category: blood group antigen]]
| |
| [[Category: glycoprotein]]
| |
| [[Category: glycosyltransferase]]
| |
| [[Category: golgi apparatus]]
| |
| [[Category: gtb abo rossman fold bbbb unliganded]]
| |
| [[Category: manganese]]
| |
| [[Category: membrane]]
| |
| [[Category: metal-binding]]
| |
| [[Category: polymorphism]]
| |
| [[Category: secreted]]
| |
| [[Category: signal-anchor]]
| |
| [[Category: transferase]]
| |
| [[Category: transmembrane]]
| |
| | |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 6 17:24:19 2008''
| |