1km2: Difference between revisions

[[Image:1km2.gif|left|200px]]<br /><applet load="1km2" size="350" color="white" frame="true" align="right" spinBox="true"  

The crystal structures of orotidine 5'-monophosphate decarboxylases from four different sources have been published recently. However, the detailed mechanism of catalysis of the most proficient enzyme known to date remains elusive. As the ligand-protein interactions at the orotate binding site are crucial to the understanding of this enzyme, we mutated several of the residues surrounding the aromatic part of the substrate, individually and in combination. The ensuing effects on enzyme structure and stability were characterized by X-ray crystallography of inhibitor, product, or substrate complexes and by chemical denaturation with guanidine hydrochloride, respectively. The results are consistent with the residues K42D70K72D75B being charged and forming an 'alternate charge network' around the reactive part of the substrate. In addition to exerting charge-charge repulsion on the orotate carboxylate, Asp70 also makes a crucial contribution to enzyme stability. Consequently, orotidine 5'-monophosphate decarboxylases seem to require the presence of a negative charge at this position for catalysis as well as for correct and stable folding.

1KM2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanothermobacter_thermautotrophicus Methanothermobacter thermautotrophicus] with <scene name='pdbligand=UP6:'>UP6</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Orotidine-5'-phosphate_decarboxylase Orotidine-5'-phosphate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.23 4.1.1.23] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KM2 OCA].  

[[Category: Pai, E F.]]

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