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< | ==Crystal Structure of Mouse Cytidine Deaminase Complexed with Cytidine== | ||
<StructureSection load='2fr6' size='340' side='right'caption='[[2fr6]], [[Resolution|resolution]] 2.07Å' scene=''> | |||
You may | == Structural highlights == | ||
or the | <table><tr><td colspan='2'>[[2fr6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FR6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FR6 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]] 2.07Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CTN:4-AMINO-1-BETA-D-RIBOFURANOSYL-2(1H)-PYRIMIDINONE'>CTN</scene>, <scene name='pdbligand=NH3:AMMONIA'>NH3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=URI:URIDINE'>URI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2fr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fr6 OCA], [https://pdbe.org/2fr6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fr6 RCSB], [https://www.ebi.ac.uk/pdbsum/2fr6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fr6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CDD_MOUSE CDD_MOUSE] This enzyme scavenge exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis (By similarity). | |||
== 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/fr/2fr6_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=2fr6 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cytidine deaminase (CDA) is a zinc-dependent enzyme that catalyzes the deamination of cytidine or deoxycytidine to form uridine or deoxyuridine. Here we present the crystal structure of mouse CDA (MmCDA), complexed with either tetrahydrouridine (THU), 3-deazauridine (DAU), or cytidine. In the MmCDA-DAU complex, it clearly demonstrates that cytidine is distinguished from uridine by its 4-NH(2) group that acts as a hydrogen bond donor. In the MmCDA-cytidine complex, cytidine, unexpectedly, binds as the substrate instead of the deaminated product in three of the four subunits, and in the remaining subunit it binds as the product uridine. Furthermore, the charge-neutralizing Arg68 of MmCDA has also exhibited two alternate conformations, I and II. In conformation I, the only conformation observed in the other structurally known homotetrameric CDAs, Arg68 hydrogen bonds Cys65 and Cys102 to modulate part of their negative charges. However, in conformation II the side chain of Arg68 rotates about 130 degrees around the Cgamma-Cdelta bond and abolishes these hydrogen bonds. The lack of hydrogen bonding may indirectly weaken the zinc-product interaction by increased electron donation from cysteine to the zinc ion, suggesting a novel product-expelling mechanism. On the basis of known structures, structural analysis further reveals two subclasses of homotetrameric CDAs that can be identified according to the position of the charge-neutralizing arginine residue. Implications for CDA-RNA interaction have also been considered. | |||
The 1.48 A resolution crystal structure of the homotetrameric cytidine deaminase from mouse.,Teh AH, Kimura M, Yamamoto M, Tanaka N, Yamaguchi I, Kumasaka T Biochemistry. 2006 Jun 27;45(25):7825-33. PMID:16784234<ref>PMID:16784234</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2fr6" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Deaminase 3D structures|Deaminase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
[[Category: | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Teh AH]] | |||
[[Category: Teh | |||
Latest revision as of 11:45, 25 October 2023
Crystal Structure of Mouse Cytidine Deaminase Complexed with CytidineCrystal Structure of Mouse Cytidine Deaminase Complexed with Cytidine
Structural highlights
FunctionCDD_MOUSE This enzyme scavenge exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis (By similarity). 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 PubMedCytidine deaminase (CDA) is a zinc-dependent enzyme that catalyzes the deamination of cytidine or deoxycytidine to form uridine or deoxyuridine. Here we present the crystal structure of mouse CDA (MmCDA), complexed with either tetrahydrouridine (THU), 3-deazauridine (DAU), or cytidine. In the MmCDA-DAU complex, it clearly demonstrates that cytidine is distinguished from uridine by its 4-NH(2) group that acts as a hydrogen bond donor. In the MmCDA-cytidine complex, cytidine, unexpectedly, binds as the substrate instead of the deaminated product in three of the four subunits, and in the remaining subunit it binds as the product uridine. Furthermore, the charge-neutralizing Arg68 of MmCDA has also exhibited two alternate conformations, I and II. In conformation I, the only conformation observed in the other structurally known homotetrameric CDAs, Arg68 hydrogen bonds Cys65 and Cys102 to modulate part of their negative charges. However, in conformation II the side chain of Arg68 rotates about 130 degrees around the Cgamma-Cdelta bond and abolishes these hydrogen bonds. The lack of hydrogen bonding may indirectly weaken the zinc-product interaction by increased electron donation from cysteine to the zinc ion, suggesting a novel product-expelling mechanism. On the basis of known structures, structural analysis further reveals two subclasses of homotetrameric CDAs that can be identified according to the position of the charge-neutralizing arginine residue. Implications for CDA-RNA interaction have also been considered. The 1.48 A resolution crystal structure of the homotetrameric cytidine deaminase from mouse.,Teh AH, Kimura M, Yamamoto M, Tanaka N, Yamaguchi I, Kumasaka T Biochemistry. 2006 Jun 27;45(25):7825-33. PMID:16784234[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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