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| {{STRUCTURE_1h7n| PDB=1h7n | SCENE= }} | | {{STRUCTURE_1h7n| PDB=1h7n | SCENE= }} |
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| '''SCHIFF-BASE COMPLEX OF YEAST 5-AMINOLAEVULINIC ACID DEHYDRATASE WITH LAEVULINIC ACID AT 1.6 A RESOLUTION'''
| | ===SCHIFF-BASE COMPLEX OF YEAST 5-AMINOLAEVULINIC ACID DEHYDRATASE WITH LAEVULINIC ACID AT 1.6 A RESOLUTION=== |
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| ==Overview==
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| The structures of 5-aminolaevulinic acid dehydratase (ALAD) complexed with substrate (5-aminolaevulinic acid) and three inhibitors: laevulinic acid, succinylacetone and 4-keto-5-aminolaevulinic acid, have been solved at high resolution. The ligands all bind by forming a covalent link with Lys263 at the active site. The structures define the interactions made by one of the two substrate moieties that bind to the enzyme during catalysis. All of the inhibitors induce a significant ordering of the flap covering the active site. Succinylacetone appears to be unique by inducing a number of conformational changes in loops covering the active site, which may be important for understanding the co-operative properties of ALAD enzymes. Succinylacetone is produced in large amounts by patients suffering from the hereditary disease type I tyrosinaemia and its potent inhibition of ALAD also has implications for the pathology of this disease. The most intriguing result is that obtained with 4-keto-5-amino-hexanoic acid, which seems to form a stable carbinolamine intermediate with Lys263. It appears that we have defined the structure of an intermediate of Schiff base formation that the substrate forms upon binding to the P-site of the enzyme. | | The line below this paragraph, {{ABSTRACT_PUBMED_11545591}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11545591 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11545591}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Tetrapyrrole synthesis]] | | [[Category: Tetrapyrrole synthesis]] |
| [[Category: Tim barrel]] | | [[Category: Tim barrel]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:32:25 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 06:45:39 2008'' |
