4ld2: Difference between revisions
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The | ==Crystal structure of NE0047 in complex with cytidine== | ||
<StructureSection load='4ld2' size='340' side='right'caption='[[4ld2]], [[Resolution|resolution]] 1.55Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ld2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Nitrosomonas_europaea_ATCC_19718 Nitrosomonas europaea ATCC 19718]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LD2 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]] 1.55Å</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=EDO:1,2-ETHANEDIOL'>EDO</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=4ld2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ld2 OCA], [https://pdbe.org/4ld2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ld2 RCSB], [https://www.ebi.ac.uk/pdbsum/4ld2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ld2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q82Y41_NITEU Q82Y41_NITEU] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Guanine deaminases (GDs) are important enzymes involved in purine metabolism as well as nucleotide anabolism pathways that exhibit a high degree of fidelity. Here, the structural basis of the substrate specificity of GDs was investigated by determining a series of X-ray structures of NE0047 (GD from Nitrosomonas europaea) with nucleobase analogues and nucleosides. The structures demonstrated that the interactions in the GD active site are tailor-made to accommodate only guanine and any substitutions in the purine ring or introduction of a pyrimidine ring results in rearrangement of the bases in a catalytically unfavorable orientation, away from the proton shuttling residue E143. In addition, X-ray structural studies performed on cytidine revealed that although it binds in an optimal conformation, its deamination does not occur because of the inability of the enzyme to orchestrate the closure of the catalytically important C-terminal loop (residues 181-189). Isothermal calorimetry measurements established that these nucleoside moieties also disrupt the sequential mode of ligand binding, thereby abrogating all intersubunit communication. Intriguingly, it was recently discovered that GDs can also serve as endogenous ammeline deaminases, although it is structurally nonhomologous with guanine. To understand the mechanism of dual-substrate specificity, the structure of NE0047 in complex with ammeline was determined to a resolution of 2.7 A. The structure revealed that ammeline not only fits in the active site in a catalytically favorable orientation but also allows for closure of the C-terminal loop. | |||
Structural basis of the substrate specificity of cytidine deaminase superfamily Guanine deaminase.,Bitra A, Biswas A, Anand R Biochemistry. 2013 Nov 12;52(45):8106-14. doi: 10.1021/bi400818e. Epub 2013 Oct, 28. PMID:24083949<ref>PMID:24083949</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4ld2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Deaminase 3D structures|Deaminase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Nitrosomonas europaea ATCC 19718]] | |||
[[Category: Anand R]] | |||
[[Category: Biswas A]] | |||
[[Category: Bitra A]] | |||
Latest revision as of 17:34, 8 November 2023
Crystal structure of NE0047 in complex with cytidineCrystal structure of NE0047 in complex with cytidine
Structural highlights
FunctionPublication Abstract from PubMedGuanine deaminases (GDs) are important enzymes involved in purine metabolism as well as nucleotide anabolism pathways that exhibit a high degree of fidelity. Here, the structural basis of the substrate specificity of GDs was investigated by determining a series of X-ray structures of NE0047 (GD from Nitrosomonas europaea) with nucleobase analogues and nucleosides. The structures demonstrated that the interactions in the GD active site are tailor-made to accommodate only guanine and any substitutions in the purine ring or introduction of a pyrimidine ring results in rearrangement of the bases in a catalytically unfavorable orientation, away from the proton shuttling residue E143. In addition, X-ray structural studies performed on cytidine revealed that although it binds in an optimal conformation, its deamination does not occur because of the inability of the enzyme to orchestrate the closure of the catalytically important C-terminal loop (residues 181-189). Isothermal calorimetry measurements established that these nucleoside moieties also disrupt the sequential mode of ligand binding, thereby abrogating all intersubunit communication. Intriguingly, it was recently discovered that GDs can also serve as endogenous ammeline deaminases, although it is structurally nonhomologous with guanine. To understand the mechanism of dual-substrate specificity, the structure of NE0047 in complex with ammeline was determined to a resolution of 2.7 A. The structure revealed that ammeline not only fits in the active site in a catalytically favorable orientation but also allows for closure of the C-terminal loop. Structural basis of the substrate specificity of cytidine deaminase superfamily Guanine deaminase.,Bitra A, Biswas A, Anand R Biochemistry. 2013 Nov 12;52(45):8106-14. doi: 10.1021/bi400818e. Epub 2013 Oct, 28. PMID:24083949[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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