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| {{STRUCTURE_2bpq| PDB=2bpq | SCENE= }} | | {{STRUCTURE_2bpq| PDB=2bpq | SCENE= }} |
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| '''ANTHRANILATE PHOSPHORIBOSYLTRANSFERASE (TRPD) FROM MYCOBACTERIUM TUBERCULOSIS (APO STRUCTURE)'''
| | ===ANTHRANILATE PHOSPHORIBOSYLTRANSFERASE (TRPD) FROM MYCOBACTERIUM TUBERCULOSIS (APO STRUCTURE)=== |
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| ==Overview==
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| Mycobacterium tuberculosis, the cause of tuberculosis, presents a major threat to human health worldwide. Biosynthetic enzymes that are essential for the survival of the bacterium, especially in activated macrophages, are important potential drug targets. Although the tryptophan biosynthesis pathway is thought to be non-essential for many pathogens, this appears not to be the case for M.tuberculosis, where a trpD gene knockout fails to cause disease in mice. We therefore chose the product of the trpD gene, anthranilate phosphoribosyltransferase, which catalyses the second step in tryptophan biosynthesis, for structural analysis. The structure of TrpD from M.tuberculosis was solved by X-ray crystallography, at 1.9 A resolution for the native enzyme (R = 0.191, Rfree = 0.230) and at 2.3 A resolution for the complex with its substrate phosphoribosylpyrophosphate (PRPP) and Mg2+ (R = 0.194, Rfree = 0.255). The enzyme is folded into two domains, separated by a hinge region. PRPP binds in the C-terminal domain, together with a pair of Mg ions. In the substrate complex, two flexible loops change conformation compared with the apo protein, to close over the PRPP and to complete an extensive network of hydrogen-bonded interactions. A nearby pocket, adjacent to the hinge region, is postulated by in silico docking as the binding site for anthranilate. A bound molecule of benzamidine, which was essential for crystallization and is also found in the hinge region, appears to reduce flexibility between the two domains.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16337227}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16337227 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16337227}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Transferase phosphoribosyltransferase]] | | [[Category: Transferase phosphoribosyltransferase]] |
| [[Category: Tryptophan biosynthesis]] | | [[Category: Tryptophan biosynthesis]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:37:24 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:18:01 2008'' |