3KDZ
X-ray crystal structure of a tyrosine aminomutase mutant construct with bound ligand
Summary for 3KDZ
| Entry DOI | 10.2210/pdb3kdz/pdb |
| Related | 2OHY 2QVE 2RJR 2RJS 3KDY |
| Descriptor | Histidine ammonia-lyase, TYROSINE (3 entities in total) |
| Functional Keywords | mio, aminomutase, enediyne, transferase, histidine metabolism, lyase |
| Biological source | Streptomyces globisporus |
| Total number of polymer chains | 2 |
| Total formula weight | 116667.91 |
| Authors | Cooke, H.A.,Bruner, S.D. (deposition date: 2009-10-23, release date: 2010-07-07, Last modification date: 2024-10-30) |
| Primary citation | Cooke, H.A.,Bruner, S.D. Probing the active site of MIO-dependent aminomutases, key catalysts in the biosynthesis of beta-amino acids incorporated in secondary metabolites Biopolymers, 93:802-810, 2010 Cited by PubMed Abstract: The tyrosine aminomutase SgTAM produces (S)-ss-tyrosine from L-tyrosine in the biosynthesis of the enediyne antitumor antibiotic C-1027. This conversion is promoted by the methylideneimidazole-5-one (MIO) prosthetic group. MIO was first identified in the homologous family of ammonia lyases, which deaminate aromatic amino acids to form alpha,ss-unsaturated carboxylates. Studies of substrate specificity have been described for lyases but there have been limited reports in altering the substrate specificity of aminomutases. Furthermore, it remains unclear as to what structural properties are responsible for catalyzing the presumed readdition of the amino group into the alpha,ss-unsaturated intermediates to form ss-amino acids. Attempts to elucidate specificity and mechanistic determinants of SgTAM have also proved to be difficult as it is recalcitrant to perturbations to the active site via mutagenesis. An X-ray cocrystal structure of the SgTAM mutant of the catalytic base with L-tyrosine verified important substrate binding residues as well as the enzymatic base. Further mutagenesis revealed that removal of these crucial interactions renders the enzyme inactive. Proposed structural determinants for mutase activity probed via mutagenesis, time-point assays and X-ray crystallography revealed a complicated role for these residues in maintaining key quaternary structure properties that aid in catalysis. PubMed: 20577998DOI: 10.1002/bip.21500 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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