1tth: Difference between revisions

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

A detailed description of the transition that allosteric enzymes undergo constitutes a major challenge in structural biology. We have succeeded in trapping four distinct allosteric states of a mutant enzyme of Escherichia coli aspartate transcarbomylase and determining their structures by X-ray crystallography. The mutant version of aspartate transcarbamoylase in which Glu50 in the catalytic chains was replaced by Ala destabilizes the native R state and shifts the equilibrium towards the T state. This behavior allowed the use of substrate analogs such as phosphonoacetamide and malonate to trap the enzyme in T-like and R-like structures that are distinct from the T-state structure of the wild-type enzyme (as represented by the structure of the enzyme with CTP bound and the R-state structure as represented by the structure with N-(phosphonacetyl)-L-aspartate bound). These structures shed light on the nature and the order of internal structural rearrangements during the transition from the T to the R state. They also suggest an explanation for diminished activity of the E50A enzyme and for the change in reaction mechanism from ordered to random for this mutant enzyme.

1TTH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=PAL:'>PAL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Aspartate_carbamoyltransferase Aspartate carbamoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.3.2 2.1.3.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TTH OCA].  

[[Category: Baker, D P.]]

[[Category: Kantrowitz, E R.]]

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