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| | {{STRUCTURE_1xdi| PDB=1xdi | SCENE= }} | | {{STRUCTURE_1xdi| PDB=1xdi | SCENE= }} |
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| - | '''Crystal structure of LpdA (Rv3303c) from Mycobacterium tuberculosis'''
| + | ===Crystal structure of LpdA (Rv3303c) from Mycobacterium tuberculosis=== |
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| - | ==Overview==
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| - | The lpdA (Rv3303c) gene from Mycobacterium tuberculosis encoding a new member of the flavoprotein disulfide reductases was expressed in Escherichia coli, and the recombinant LpdA protein was purified to homogeneity. LpdA is a homotetramer and co-purifies with one molecule of tightly but noncovalently bound FAD and NADP+ per monomer. Although annotated as a probable lipoamide dehydrogenase in M. tuberculosis, LpdA cannot catalyze reduction of lipoyl substrates, because it lacks one of two cysteine residues involved in dithiol-disulfide interchange with lipoyl substrates and a His-Glu pair involved in general acid catalysis. The crystal structure of LpdA was solved by multiple isomorphous replacement with anomalous scattering, which confirmed the absence of these catalytic residues from the active site. Although LpdA cannot catalyze reduction of disulfide-bonded substrates, it catalyzes the NAD(P)H-dependent reduction of alternative electron acceptors such as 2,6-dimethyl-1,4-benzoquinone and 5-hydroxy-1,4-naphthaquinone. Significant primary deuterium kinetic isotope effects were observed with [4S-2H]NADH establishing that the enzyme promotes transfer of the C4-proS hydride of NADH. The absence of an isotope effect with [4S-2H]NADPH, the low Km value of 0.5 microm for NADPH, and the potent inhibition of the NADH-dependent reduction of 2,6-dimethyl-1,4-benzoquinone by NADP+ (Ki approximately 6 nm) and 2'-phospho-ADP-ribose (Ki approximately 800 nm), demonstrate the high affinity of LpdA for 2'-phosphorylated nucleotides and that the physiological substrate/product pair is NADPH/NADP+ rather than NADH/NAD+. Modeling of NADP+ in the active site revealed that LpdA achieves the high specificity for NADP+ through interactions involving the 2'-phosphate of NADP+ and amino acid residues that are different from those in glutathione reductase. | + | The line below this paragraph, {{ABSTRACT_PUBMED_15456792}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15456792 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15456792}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Nadp]] | | [[Category: Nadp]] |
| | [[Category: Reductase]] | | [[Category: Reductase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:53:27 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 23:12:29 2008'' |
Revision as of 20:12, 28 July 2008
Template:STRUCTURE 1xdi
Crystal structure of LpdA (Rv3303c) from Mycobacterium tuberculosis
Template:ABSTRACT PUBMED 15456792
About this Structure
1XDI is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
Characterization of a new member of the flavoprotein disulfide reductase family of enzymes from Mycobacterium tuberculosis., Argyrou A, Vetting MW, Blanchard JS, J Biol Chem. 2004 Dec 10;279(50):52694-702. Epub 2004 Sep 29. PMID:15456792
Page seeded by OCA on Mon Jul 28 23:12:29 2008
