Crystal structure of Glutaryl-COA dehydrogenase from Burkholderia Pseudomallei with fragment 6421Crystal structure of Glutaryl-COA dehydrogenase from Burkholderia Pseudomallei with fragment 6421

Structural highlights

3gnc is a 4 chain structure with sequence from Burkholderia pseudomallei 1710b. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.15Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q3JP94_BURP1

Evolutionary Conservation

 

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Glutaric acidemia type 1 is an inherited metabolic disorder which can cause macrocephaly, muscular rigidity, spastic paralysis and other progressive movement disorders in humans. The defects in glutaryl-CoA dehydrogenase (GCDH) associated with this disease are thought to increase holoenzyme instability and reduce cofactor binding. Here, the first structural analysis of a GCDH enzyme in the absence of the cofactor flavin adenine dinucleotide (FAD) is reported. The apo structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary structure and increased disorder in the FAD-binding pocket relative to the ternary complex of the highly homologous human GCDH. After conducting a fragment-based screen, four small molecules were identified which bind to GCDH from B. pseudomallei. Complex structures were determined for these fragments, which cause backbone and side-chain perturbations to key active-site residues. Structural insights from this investigation highlight differences from apo GCDH and the utility of small-molecular fragments as chemical probes for capturing alternative conformational states of preformed protein crystals.

Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening.,Begley DW, Davies DR, Hartley RC, Hewitt SN, Rychel AL, Myler PJ, Van Voorhis WC, Staker BL, Stewart LJ Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Sep 1;67(Pt, 9):1060-9. Epub 2011 Aug 13. PMID:21904051[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Begley DW, Davies DR, Hartley RC, Hewitt SN, Rychel AL, Myler PJ, Van Voorhis WC, Staker BL, Stewart LJ. Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Sep 1;67(Pt, 9):1060-9. Epub 2011 Aug 13. PMID:21904051 doi:10.1107/S1744309111014436

3gnc, resolution 2.15Å

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