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[[Image:2bh9.gif|left|200px]]<br />
<applet load="2bh9" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2bh9, resolution 2.50&Aring;" />
'''X-RAY STRUCTURE OF A DELETION VARIANT OF HUMAN GLUCOSE 6-PHOSPHATE DEHYDROGENASE COMPLEXED WITH STRUCTURAL AND COENZYME NADP'''<br />


==Overview==
==X-RAY STRUCTURE OF A DELETION VARIANT OF HUMAN GLUCOSE 6-PHOSPHATE DEHYDROGENASE COMPLEXED WITH STRUCTURAL AND COENZYME NADP==
Human glucose-6-phosphate dehydrogenase (G6PD) is NADP(+)-dependent and, catalyses the first and rate-limiting step of the pentose phosphate shunt., Binary complexes of the human deletion mutant, DeltaG6PD, with, glucose-6-phosphate and NADP(+) have been crystallized and their, structures solved to 2.9 and 2.5 A, respectively. The structures are, compared with the previously determined structure of the Canton variant of, human G6PD (G6PD(Canton)) in which NADP(+) is bound at the structural, site. Substrate binding in DeltaG6PD is shown to be very similar to that, described previously in Leuconostoc mesenteroides G6PD. NADP(+) binding at, the coenzyme site is seen to be comparable to NADP(+) binding in L., mesenteroides G6PD, although some differences arise as a result of, sequence changes. The tetramer interface varies slightly among the human, G6PD complexes, suggesting flexibility in the predominantly hydrophilic, dimer-dimer interactions. In both complexes, Pro172 of the conserved, peptide EKPxG is in the cis conformation; it is seen to be crucial for, close approach of the substrate and coenzyme during the enzymatic, reaction. Structural NADP(+) binds in a very similar way in the, DeltaG6PD-NADP(+) complex and in G6PD(Canton), while in the substrate, complex the structural NADP(+) has low occupancy and the C-terminal tail, at the structural NADP(+) site is disordered. The implications of possible, interaction between the structural NADP(+) and G6P are considered.
<StructureSection load='2bh9' size='340' side='right'caption='[[2bh9]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2bh9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BH9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BH9 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2bh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bh9 OCA], [https://pdbe.org/2bh9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bh9 RCSB], [https://www.ebi.ac.uk/pdbsum/2bh9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bh9 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/G6PD_HUMAN G6PD_HUMAN] Defects in G6PD are the cause of chronic non-spherocytic hemolytic anemia (CNSHA) [MIM:[https://omim.org/entry/305900 305900]. Deficiency of G6PD is associated with hemolytic anemia in two different situations. First, in areas in which malaria has been endemic, G6PD-deficiency alleles have reached high frequencies (1% to 50%) and deficient individuals, though essentially asymptomatic in the steady state, have a high risk of acute hemolytic attacks. Secondly, sporadic cases of G6PD deficiency occur at a very low frequencies, and they usually present a more severe phenotype. Several types of CNSHA are recognized. Class-I variants are associated with severe NSHA; class-II have an activity <10% of normal; class-III have an activity of 10% to 60% of normal; class-IV have near normal activity.<ref>PMID:1611091</ref>
== Function ==
[https://www.uniprot.org/uniprot/G6PD_HUMAN G6PD_HUMAN] Produces pentose sugars for nucleic acid synthesis and main producer of NADPH reducing power.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bh/2bh9_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2bh9 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2BH9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAP and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glucose-6-phosphate_1-dehydrogenase Glucose-6-phosphate 1-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.49 1.1.1.49] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BH9 OCA].
*[[Glucose 6-phosphate dehydrogenase|Glucose 6-phosphate dehydrogenase]]
 
== References ==
==Reference==
<references/>
Structural studies of glucose-6-phosphate and NADP+ binding to human glucose-6-phosphate dehydrogenase., Kotaka M, Gover S, Vandeputte-Rutten L, Au SW, Lam VM, Adams MJ, Acta Crystallogr D Biol Crystallogr. 2005 May;61(Pt 5):495-504. Epub 2005, Apr 20. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15858258 15858258]
__TOC__
[[Category: Glucose-6-phosphate 1-dehydrogenase]]
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Adams, M.J.]]
[[Category: Adams MJ]]
[[Category: Au, S.W.N.]]
[[Category: Au SWN]]
[[Category: Gover, S.]]
[[Category: Gover S]]
[[Category: Vandeputte-Rutten, L.]]
[[Category: Vandeputte-Rutten L]]
[[Category: GOL]]
[[Category: NAP]]
[[Category: carbohydrate metabolism]]
[[Category: glucose metabolism]]
[[Category: oxidoreductase (choh(d)-nadp)]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov  5 13:55:21 2007''

Latest revision as of 09:38, 1 May 2024

X-RAY STRUCTURE OF A DELETION VARIANT OF HUMAN GLUCOSE 6-PHOSPHATE DEHYDROGENASE COMPLEXED WITH STRUCTURAL AND COENZYME NADPX-RAY STRUCTURE OF A DELETION VARIANT OF HUMAN GLUCOSE 6-PHOSPHATE DEHYDROGENASE COMPLEXED WITH STRUCTURAL AND COENZYME NADP

Structural highlights

2bh9 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

G6PD_HUMAN Defects in G6PD are the cause of chronic non-spherocytic hemolytic anemia (CNSHA) [MIM:305900. Deficiency of G6PD is associated with hemolytic anemia in two different situations. First, in areas in which malaria has been endemic, G6PD-deficiency alleles have reached high frequencies (1% to 50%) and deficient individuals, though essentially asymptomatic in the steady state, have a high risk of acute hemolytic attacks. Secondly, sporadic cases of G6PD deficiency occur at a very low frequencies, and they usually present a more severe phenotype. Several types of CNSHA are recognized. Class-I variants are associated with severe NSHA; class-II have an activity <10% of normal; class-III have an activity of 10% to 60% of normal; class-IV have near normal activity.[1]

Function

G6PD_HUMAN Produces pentose sugars for nucleic acid synthesis and main producer of NADPH reducing power.

Evolutionary Conservation

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

See Also

References

  1. ↑ Beutler E, Westwood B, Prchal JT, Vaca G, Bartsocas CS, Baronciani L. New glucose-6-phosphate dehydrogenase mutations from various ethnic groups. Blood. 1992 Jul 1;80(1):255-6. PMID:1611091

2bh9, resolution 2.50Å

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