1pvn: Difference between revisions

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{{Seed}}
[[Image:1pvn.png|left|200px]]


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==The crystal structure of the complex between IMP dehydrogenase catalytic domain and a transition state analogue MZP==
The line below this paragraph, containing "STRUCTURE_1pvn", creates the "Structure Box" on the page.
<StructureSection load='1pvn' size='340' side='right'caption='[[1pvn]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1pvn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Tritrichomonas_suis Tritrichomonas suis]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1mwf 1mwf]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PVN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PVN FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</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&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MZP:4-CARBAMOYL-1-BETA-D-RIBOFURANOSYL-IMIDAZOLIUM-5-OLATE-5-PHOSPHATE'>MZP</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
{{STRUCTURE_1pvn|  PDB=1pvn  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1pvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pvn OCA], [https://pdbe.org/1pvn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pvn RCSB], [https://www.ebi.ac.uk/pdbsum/1pvn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pvn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IMDH_TRIFO IMDH_TRIFO] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism.<ref>PMID:10029522</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/pv/1pvn_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=1pvn ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mizoribine monophosphate (MZP) is the active metabolite of the immunosuppressive agent mizoribine and a potent inhibitor of IMP dehydrogenase (IMPDH). This enzyme catalyzes the oxidation of IMP to XMP with the concomitant reduction of NAD via a covalent intermediate at Cys319 (E-XMP). Surprisingly, mutational analysis indicates that MZP is a transition state analogue although its structure does not resemble that of the expected transition state. Here we report the X-ray crystal structure of the E.MZP complex at 2.0 A resolution that reveals a transition state-like structure and solves the mechanistic puzzle of the IMPDH reaction. The protein assumes a new conformation where a flap folds into the NAD site and MZP, Cys319, and a water molecule are arranged in a geometry resembling the transition state. The water appears to be activated by interactions with a conserved Arg418-Tyr419 dyad. Mutagenesis experiments confirm that this new closed conformation is required for the hydrolysis of E-XMP, but not for the reduction of NAD. The closed conformation provides a structural explanation for the differences in drug selectivity and catalytic efficiency of IMPDH isozymes.


===The crystal structure of the complex between IMP dehydrogenase catalytic domain and a transition state analogue MZP===
The immunosuppressive agent mizoribine monophosphate forms a transition state analogue complex with inosine monophosphate dehydrogenase.,Gan L, Seyedsayamdost MR, Shuto S, Matsuda A, Petsko GA, Hedstrom L Biochemistry. 2003 Feb 4;42(4):857-63. PMID:12549902<ref>PMID:12549902</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1pvn" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_12549902}}, adds the Publication Abstract to the page
*[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 12549902 is the PubMed ID number.
== References ==
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<references/>
{{ABSTRACT_PUBMED_12549902}}
__TOC__
 
</StructureSection>
==About this Structure==
[[Category: Large Structures]]
1PVN is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Tritrichomonas_foetus Tritrichomonas foetus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1mwf 1mwf]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PVN OCA].
[[Category: Tritrichomonas suis]]
 
[[Category: Gan L]]
==Reference==
[[Category: Hedstrom L]]
<ref group="xtra">PMID:12549902</ref><references group="xtra"/>
[[Category: Matsuda A]]
[[Category: IMP dehydrogenase]]
[[Category: Petsko GA]]
[[Category: Tritrichomonas foetus]]
[[Category: Seyedsayamdost M]]
[[Category: Gan, L.]]
[[Category: Shuto S]]
[[Category: Hedstrom, L.]]
[[Category: Matsuda, A.]]
[[Category: Petsko, G A.]]
[[Category: Seyedsayamdost, M.]]
[[Category: Shuto, S.]]
[[Category: Distal flap]]
[[Category: Drug selectivity]]
[[Category: General base]]
[[Category: Imp dehydrogenase]]
[[Category: Mizoribine 5'-monophosphate]]
[[Category: Transition state analogue]]
 
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Retrieved from "https://proteopedia.org/1pvn"