2c6q: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| (22 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==Crystal structure of human guanosine monophosphate reductase 2 GMPR2 in complex with IMP and NADPH== | ||
<StructureSection load='2c6q' size='340' side='right'caption='[[2c6q]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2c6q]] is a 8 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=2C6Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C6Q 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]] 1.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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=2c6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c6q OCA], [https://pdbe.org/2c6q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c6q RCSB], [https://www.ebi.ac.uk/pdbsum/2c6q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c6q ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GMPR2_HUMAN GMPR2_HUMAN] Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides. Plays a role in modulating cellular differentiation.<ref>PMID:12009299</ref> <ref>PMID:12669231</ref> | |||
== 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/c6/2c6q_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2c6q ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Inosine monophosphate dehydrogenase (IMPDH) and guanosine monophosphate reductase (GMPR) belong to the same structural family, share a common set of catalytic residues and bind the same ligands. The structural and mechanistic features that determine reaction outcome in the IMPDH and GMPR family have not been identified. Here we show that the GMPR reaction uses the same intermediate E-XMP* as IMPDH, but in this reaction the intermediate reacts with ammonia instead of water. A single crystal structure of human GMPR type 2 with IMP and NADPH fortuitously captures three different states, each of which mimics a distinct step in the catalytic cycle of GMPR. The cofactor is found in two conformations: an 'in' conformation poised for hydride transfer and an 'out' conformation in which the cofactor is 6 A from IMP. Mutagenesis along with substrate and cofactor analog experiments demonstrate that the out conformation is required for the deamination of GMP. Remarkably, the cofactor is part of the catalytic machinery that activates ammonia. | |||
Cofactor mobility determines reaction outcome in the IMPDH and GMPR (beta-alpha)(8) barrel enzymes.,Patton GC, Stenmark P, Gollapalli DR, Sevastik R, Kursula P, Flodin S, Schuler H, Swales CT, Eklund H, Himo F, Nordlund P, Hedstrom L Nat Chem Biol. 2011 Oct 30;7(12):950-8. doi: 10.1038/nchembio.693. PMID:22037469<ref>PMID:22037469</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2c6q" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Arrowsmith | [[Category: Arrowsmith C]] | ||
[[Category: Berglund | [[Category: Berglund H]] | ||
[[Category: Edwards | [[Category: Edwards A]] | ||
[[Category: Ehn | [[Category: Ehn M]] | ||
[[Category: Graslund | [[Category: Graslund S]] | ||
[[Category: Hallberg | [[Category: Hallberg BM]] | ||
[[Category: Hammarstrom | [[Category: Hammarstrom M]] | ||
[[Category: Kotenyova | [[Category: Kotenyova T]] | ||
[[Category: Kursula | [[Category: Kursula P]] | ||
[[Category: Nilsson-Ehle | [[Category: Nilsson-Ehle P]] | ||
[[Category: Nordlund | [[Category: Nordlund P]] | ||
[[Category: Ogg | [[Category: Ogg D]] | ||
[[Category: Persson | [[Category: Persson C]] | ||
[[Category: Sagemark | [[Category: Sagemark J]] | ||
[[Category: Schuler | [[Category: Schuler H]] | ||
[[Category: Stenmark | [[Category: Stenmark P]] | ||
[[Category: Sundstrom | [[Category: Sundstrom M]] | ||
[[Category: Thorsell | [[Category: Thorsell A]] | ||
[[Category: Weigelt | [[Category: Weigelt J]] | ||
Latest revision as of 10:48, 23 October 2024
Crystal structure of human guanosine monophosphate reductase 2 GMPR2 in complex with IMP and NADPHCrystal structure of human guanosine monophosphate reductase 2 GMPR2 in complex with IMP and NADPH
Structural highlights
FunctionGMPR2_HUMAN Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides. Plays a role in modulating cellular differentiation.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedInosine monophosphate dehydrogenase (IMPDH) and guanosine monophosphate reductase (GMPR) belong to the same structural family, share a common set of catalytic residues and bind the same ligands. The structural and mechanistic features that determine reaction outcome in the IMPDH and GMPR family have not been identified. Here we show that the GMPR reaction uses the same intermediate E-XMP* as IMPDH, but in this reaction the intermediate reacts with ammonia instead of water. A single crystal structure of human GMPR type 2 with IMP and NADPH fortuitously captures three different states, each of which mimics a distinct step in the catalytic cycle of GMPR. The cofactor is found in two conformations: an 'in' conformation poised for hydride transfer and an 'out' conformation in which the cofactor is 6 A from IMP. Mutagenesis along with substrate and cofactor analog experiments demonstrate that the out conformation is required for the deamination of GMP. Remarkably, the cofactor is part of the catalytic machinery that activates ammonia. Cofactor mobility determines reaction outcome in the IMPDH and GMPR (beta-alpha)(8) barrel enzymes.,Patton GC, Stenmark P, Gollapalli DR, Sevastik R, Kursula P, Flodin S, Schuler H, Swales CT, Eklund H, Himo F, Nordlund P, Hedstrom L Nat Chem Biol. 2011 Oct 30;7(12):950-8. doi: 10.1038/nchembio.693. PMID:22037469[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||