1xdi
From Proteopedia
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|PDB= 1xdi |SIZE=350|CAPTION= <scene name='initialview01'>1xdi</scene>, resolution 2.81Å | |PDB= 1xdi |SIZE=350|CAPTION= <scene name='initialview01'>1xdi</scene>, resolution 2.81Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE DINUCLEOTIDE'>FAD</scene> | + | |LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= Rv3303c - lpdA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]) | |GENE= Rv3303c - lpdA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xdi OCA], [http://www.ebi.ac.uk/pdbsum/1xdi PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xdi RCSB]</span> | ||
}} | }} | ||
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[[Category: Blanchard, J S.]] | [[Category: Blanchard, J S.]] | ||
[[Category: Vetting, M W.]] | [[Category: Vetting, M W.]] | ||
| - | [[Category: FAD]] | ||
[[Category: fad]] | [[Category: fad]] | ||
[[Category: mycobacterium tuberculosis]] | [[Category: mycobacterium tuberculosis]] | ||
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[[Category: reductase]] | [[Category: reductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:48:07 2008'' |
Revision as of 21:48, 30 March 2008
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| , resolution 2.81Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | Rv3303c - lpdA (Mycobacterium tuberculosis) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of LpdA (Rv3303c) from Mycobacterium tuberculosis
Overview
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.
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
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