4lco: Difference between revisions
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==Crystal structure of NE0047 with complex with substrate ammeline== | |||
=== | <StructureSection load='4lco' size='340' side='right' caption='[[4lco]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4lco]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Niteu Niteu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LCO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LCO FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6AM:4,6-DIAMINO-1,3,5-TRIAZIN-2-OL'>6AM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hrq|4hrq]], [[4hrw|4hrw]], [[2g84|2g84]], [[4lc5|4lc5]], [[4lcn|4lcn]], [[4lcp|4lcp]], [[4ld2|4ld2]], [[4ld4|4ld4]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NE0047 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=228410 NITEU])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4lco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lco OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lco RCSB], [http://www.ebi.ac.uk/pdbsum/4lco PDBsum]</span></td></tr> | |||
</table> | |||
<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> | |||
[[Category: Anand, R | == References == | ||
[[Category: Biswas, A | <references/> | ||
[[Category: Bitra, A | __TOC__ | ||
</StructureSection> | |||
[[Category: Niteu]] | |||
[[Category: Anand, R]] | |||
[[Category: Biswas, A]] | |||
[[Category: Bitra, A]] | |||
[[Category: Cda fold]] | [[Category: Cda fold]] | ||
[[Category: Deaminase]] | [[Category: Deaminase]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
Revision as of 20:12, 21 December 2014
Crystal structure of NE0047 with complex with substrate ammelineCrystal structure of NE0047 with complex with substrate ammeline
Structural highlights
Publication 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. References
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