2vyv

From Proteopedia

(Difference between revisions)

Current revision

Structure of E.Coli GAPDH Rat Sperm GAPDH heterotetramer

Structural highlights

2vyv is a 4 chain structure with sequence from Escherichia coli BL21(DE3) and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.38Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

G3P1_ECOLI

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

Sperm glyceraldehyde-3-phosphate dehydrogenase has been shown to be a successful target for a non-hormonal contraceptive approach, but the agents tested to date have had unacceptable side effects. Obtaining the structure of the sperm-specific isoform to allow rational inhibitor design has therefore been a goal for a number of years but has proved intractable because of the insoluble nature of both native and recombinant protein. We have obtained soluble recombinant sperm glyceraldehyde-3-phosphate dehydrogenase as a heterotetramer with the Escherichia coli glyceraldehyde-3-phosphate dehydrogenase in a ratio of 1:3 and have solved the structure of the heterotetramer which we believe represents a novel strategy for structure determination of an insoluble protein. A structure was also obtained where glyceraldehyde 3-phosphate binds in the P(s) pocket in the active site of the sperm enzyme subunit in the presence of NAD. Modeling and comparison of the structures of human somatic and sperm-specific glyceraldehyde-3-phosphate dehydrogenase revealed few differences at the active site and hence rebut the long presumed structural specificity of 3-chlorolactaldehyde for the sperm isoform. The contraceptive activity of alpha-chlorohydrin and its apparent specificity for the sperm isoform in vivo are likely to be due to differences in metabolism to 3-chlorolactaldehyde in spermatozoa and somatic cells. However, further detailed analysis of the sperm glyceraldehyde-3-phosphate dehydrogenase structure revealed sites in the enzyme that do show significant difference compared with published somatic glyceraldehyde-3-phosphate dehydrogenase structures that could be exploited by structure-based drug design to identify leads for novel male contraceptives.

Structure of insoluble rat sperm glyceraldehyde-3-phosphate dehydrogenase (GAPDH) via heterotetramer formation with Escherichia coli GAPDH reveals target for contraceptive design.,Frayne J, Taylor A, Cameron G, Hadfield AT J Biol Chem. 2009 Aug 21;284(34):22703-12. Epub 2009 Jun 19. PMID:19542219^[1]

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

References

↑ Frayne J, Taylor A, Cameron G, Hadfield AT. Structure of insoluble rat sperm glyceraldehyde-3-phosphate dehydrogenase (GAPDH) via heterotetramer formation with Escherichia coli GAPDH reveals target for contraceptive design. J Biol Chem. 2009 Aug 21;284(34):22703-12. Epub 2009 Jun 19. PMID:19542219 doi:10.1074/jbc.M109.004648

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/2vyv"

@@ Line 3: / Line 3: @@
 <StructureSection load='2vyv' size='340' side='right'caption='[[2vyv]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2vyv]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli_bl21(de3) Escherichia coli bl21(de3)] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VYV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2VYV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2vyv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_BL21(DE3) Escherichia coli BL21(DE3)] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VYV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1GP:SN-GLYCEROL-1-PHOSPHATE'>1GP</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1GP:SN-GLYCEROL-1-PHOSPHATE'>1GP</scene>, <scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dc6|1dc6]], [[1dc4|1dc4]], [[1dc3|1dc3]], [[2vyn|2vyn]], [[1s7c|1s7c]], [[1dc5|1dc5]], [[1gad|1gad]], [[1gae|1gae]]</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=2vyv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vyv OCA], [https://pdbe.org/2vyv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vyv RCSB], [https://www.ebi.ac.uk/pdbsum/2vyv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vyv ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glyceraldehyde-3-phosphate_dehydrogenase_(phosphorylating) Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.12 1.2.1.12] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2vyv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vyv OCA], [http://pdbe.org/2vyv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vyv RCSB], [http://www.ebi.ac.uk/pdbsum/2vyv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vyv ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/G3P1_ECOLI G3P1_ECOLI]
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 39: / Line 39: @@
 [[Category: Large Structures]]
 [[Category: Rattus norvegicus]]
-[[Category: Frayne, J]]
+[[Category: Frayne J]]
-[[Category: Hadfield, A]]
+[[Category: Hadfield A]]
-[[Category: Hall, L]]
+[[Category: Hall L]]
-[[Category: Taylor, A]]
+[[Category: Taylor A]]
-[[Category: Alpha chlorohydrin]]
-[[Category: Contraceptive]]
-[[Category: Cytoplasm]]
-[[Category: Gapdh]]
-[[Category: Glyceraldehyde-3-phosphate]]
-[[Category: Glycolysis]]
-[[Category: Nad]]
-[[Category: Oxidoreductase]]
-[[Category: Rat sperm]]

2vyv

From Proteopedia

Current revision

Structure of E.Coli GAPDH Rat Sperm GAPDH heterotetramer

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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