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1qki
From Proteopedia
| 1qki, resolution 3.00Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Sites: | , , , , , , , , , , , , , , , , , , , and | ||||||||
| Ligands: | , , | ||||||||
| Gene: | G6PD (Homo sapiens) | ||||||||
| Activity: | Glucose-6-phosphate dehydrogenase, with EC number 1.1.1.49 | ||||||||
| Related: | 1dpg, 2dpg | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
X-RAY STRUCTURE OF HUMAN GLUCOSE 6-PHOSPHATE DEHYDROGENASE (VARIANT CANTON R459L) COMPLEXED WITH STRUCTURAL NADP+
BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) catalyses the first committed step in the pentose phosphate pathway; the generation of NADPH by this enzyme is essential for protection against oxidative stress. The human enzyme is in a dimer<-->tetramer equilibrium and its stability is dependent on NADP(+) concentration. G6PD deficiency results from many different point mutations in the X-linked gene encoding G6PD and is the most common human enzymopathy. Severe deficiency causes chronic non-spherocytic haemolytic anaemia; the usual symptoms are neonatal jaundice, favism and haemolytic anaemia. RESULTS: We have determined the first crystal structure of a human G6PD (the mutant Canton, Arg459-->Leu) at 3 A resolution. The tetramer is a dimer of dimers. Despite very similar dimer topology, there are two major differences from G6PD of Leuconostoc mesenteroides: a structural NADP(+) molecule, close to the dimer interface but integral to the subunit, is visible in all subunits of the human enzyme; and an intrasubunit disulphide bond tethers the otherwise disordered N-terminal segment. The few dimer-dimer contacts making the tetramer are charge-charge interactions. CONCLUSIONS: The importance of NADP(+) for stability is explained by the structural NADP(+) site, which is not conserved in prokaryotes. The structure shows that point mutations causing severe deficiency predominate close to the structural NADP(+) and the dimer interface, primarily affecting the stability of the molecule. They also indicate that a stable dimer is essential to retain activity in vivo. As there is an absolute requirement for some G6PD activity, residues essential for coenzyme or substrate binding are rarely modified.
Human glucose-6-phosphate dehydrogenase: the crystal structure reveals a structural NADP(+) molecule and provides insights into enzyme deficiency., Au SW, Gover S, Lam VM, Adams MJ, Structure. 2000 Mar 15;8(3):293-303. PMID:10745013
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Disease
Known disease associated with this structure: Favism OMIM:[305900], G6PD deficiency OMIM:[305900], Hemolytic anemia due to G6PD deficiency OMIM:[305900]
About this Structure
1QKI is a 8 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Au SW, Gover S, Lam VM, Adams MJ. Human glucose-6-phosphate dehydrogenase: the crystal structure reveals a structural NADP(+) molecule and provides insights into enzyme deficiency. Structure. 2000 Mar 15;8(3):293-303. PMID:10745013
- Au SW, Naylor CE, Gover S, Vandeputte-Rutten L, Scopes DA, Mason PJ, Luzzatto L, Lam VM, Adams MJ. Solution of the structure of tetrameric human glucose 6-phosphate dehydrogenase by molecular replacement. Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):826-34. PMID:10089300
Page seeded by OCA on Wed Jun 17 20:11:58 2009
