3k5h

<StructureSection load='3k5h' size='340' side='right' caption='[[3k5h]], [[Resolution|resolution]] 2.10&Aring;' scene=''>

<table><tr><td colspan='2'>[[3k5h]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspcv Aspcv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K5H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3K5H FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3k5i|3k5i]]</td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACLA_051590, ade2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5057 ASPCV])</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoribosylaminoimidazole_carboxylase Phosphoribosylaminoimidazole carboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.21 4.1.1.21] </span></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=3k5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k5h OCA], [http://pdbe.org/3k5h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3k5h RCSB], [http://www.ebi.ac.uk/pdbsum/3k5h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3k5h ProSAT]</span></td></tr>

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== Publication Abstract from PubMed ==

N(5)-Carboxyaminoimidazole ribonucleotide synthetase (N(5)-CAIR synthetase), a key enzyme in microbial de novo purine biosynthesis, catalyzes the conversion of aminoimidazole ribonucleotide (AIR) to N(5)-CAIR. To date, this enzyme has been observed only in microorganisms, and thus, it represents an ideal target for antimicrobial drug development. Here we report the cloning, crystallization, and three-dimensional structural analysis of Aspergillus clavatus N(5)-CAIR synthetase solved in the presence of either Mg(2)ATP or MgADP and AIR. These structures, determined to 2.1 and 2.0 A, respectively, revealed that AIR binds in a pocket analogous to that observed for other ATP-grasp enzymes involved in purine metabolism. On the basis of these models, a site-directed mutagenesis study was subsequently conducted that focused on five amino acid residues located in the active site region of the enzyme. These investigations demonstrated that Asp 153 and Lys 353 play critical roles in catalysis without affecting substrate binding. All other mutations affected substrate binding and, in some instances, catalysis as well. Taken together, the structural and kinetic data presented here suggest a catalytic mechanism whereby Mg(2)ATP and bicarbonate first react to form the unstable intermediate carboxyphosphate. This intermediate subsequently decarboxylates to CO(2) and inorganic phosphate, and the amino group of AIR, through general base assistance by Asp 153, attacks CO(2) to form N(5)-CAIR.

 

== References ==

[[Category: Aspcv]]

[[Category: Phosphoribosylaminoimidazole carboxylase]]

[[Category: Firestine, S M]]

[[Category: Holden, H M]]

[[Category: Paritala, H]]

[[Category: Thoden, J B]]

[[Category: Purine biosynthesis]]