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| | ==Binary complex of Human glycerol 3-phosphate dehydrogenase with NAD== | | ==Binary complex of Human glycerol 3-phosphate dehydrogenase with NAD== |
| - | <StructureSection load='6e8z' size='340' side='right' caption='[[6e8z]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='6e8z' size='340' side='right'caption='[[6e8z]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6e8z]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E8Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E8Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6e8z]] is a 2 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=6E8Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E8Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.1Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glycerol-3-phosphate_dehydrogenase_(NAD(+)) Glycerol-3-phosphate dehydrogenase (NAD(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.8 1.1.1.8] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e8z OCA], [http://pdbe.org/6e8z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e8z RCSB], [http://www.ebi.ac.uk/pdbsum/6e8z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e8z ProSAT]</span></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=6e8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e8z OCA], [https://pdbe.org/6e8z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e8z RCSB], [https://www.ebi.ac.uk/pdbsum/6e8z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e8z ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/GPDA_HUMAN GPDA_HUMAN]] Defects in GPD1 are a cause of hypertriglyceridemia, transient infantile (HTGTI) [MIM:[http://omim.org/entry/614480 614480]]. An autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis.<ref>PMID:22226083</ref> | + | [https://www.uniprot.org/uniprot/GPDA_HUMAN GPDA_HUMAN] Defects in GPD1 are a cause of hypertriglyceridemia, transient infantile (HTGTI) [MIM:[https://omim.org/entry/614480 614480]. An autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis.<ref>PMID:22226083</ref> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/GPDA_HUMAN GPDA_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6e8z" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6e8z" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glycerol-3-phosphate dehydrogenase 3D structures|Glycerol-3-phosphate dehydrogenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Gulick, A M]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Mydy, L S]] | + | [[Category: Large Structures]] |
| - | [[Category: Oxidoreductase]] | + | [[Category: Gulick AM]] |
| | + | [[Category: Mydy LS]] |
| Structural highlights
Disease
GPDA_HUMAN Defects in GPD1 are a cause of hypertriglyceridemia, transient infantile (HTGTI) [MIM:614480. An autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis.[1]
Function
GPDA_HUMAN
Publication Abstract from PubMed
Human liver glycerol-3-phosphate dehydrogenase (hlGPDH) catalyzes the reduction of dihydroxacetone phosphate (DHAP) to form glycerol 3-phosphate, using the binding energy associated with the nonreacting phosphodianion of the substrate to properly orient the enzyme-substrate complex within the active site. Herein, we report the crystal structures for unliganded, binary E*NAD, and ternary E*NAD*DHAP complexes of wild type hlGPDH, illustrating a new position of DHAP, and probe the kinetics of multiple mutant enzymes with natural and truncated substrates. Mutation of Lys120, which is positioned to donate a proton to the carbonyl of DHAP, results in similar increases in the activation barrier to hlGPDH-catlyzed reduction of DHAP and to phosphite dianion activated reduction of glycolaldehyde, illustrating that these transition states show similar interactions with the cationic K120 side chain. The K120A mutation results in a 5.3 kcal/mol transition state destabilization, and 3.0 kcal/mol of the lost transition state stabilization is rescued by 1.0 M ethylammonium cation. The 6.5 kcal/mol increase in the activation barrier observed for the D260G mutant hlGPDH-catalyzed reaction represents a 3.5 kcal/mol weakening of transition state stabilization by the K120A side chain, and a 3.0 kcal/mol weakening of the interactions with other residues. The interactions, at the enzyme active site, between the K120 side chain and the Q295 and R269 side chains was likewise examined by double mutant analyses. These results provide strong evidence that the enzyme rate acceleration is due mainly or exclusively to transition state stabilization by electrostatic interactions with polar amino acid side chains.
Human Glycerol 3-Phosphate Dehydrogenase: X-Ray Crystal Structures that Guide the Interpretation of Mutagenesis Studies.,Mydy LS, Cristobal JR, Katigbak RD, Bauer P, Reyes AC, Kamerlin SCL, Richard JP, Gulick AM Biochemistry. 2019 Jan 14. doi: 10.1021/acs.biochem.8b01103. PMID:30640445[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Basel-Vanagaite L, Zevit N, Har Zahav A, Guo L, Parathath S, Pasmanik-Chor M, McIntyre AD, Wang J, Albin-Kaplanski A, Hartman C, Marom D, Zeharia A, Badir A, Shoerman O, Simon AJ, Rechavi G, Shohat M, Hegele RA, Fisher EA, Shamir R. Transient infantile hypertriglyceridemia, fatty liver, and hepatic fibrosis caused by mutated GPD1, encoding glycerol-3-phosphate dehydrogenase 1. Am J Hum Genet. 2012 Jan 13;90(1):49-60. doi: 10.1016/j.ajhg.2011.11.028. Epub, 2012 Jan 5. PMID:22226083 doi:10.1016/j.ajhg.2011.11.028
- ↑ Mydy LS, Cristobal JR, Katigbak RD, Bauer P, Reyes AC, Kamerlin SCL, Richard JP, Gulick AM. Human Glycerol 3-Phosphate Dehydrogenase: X-Ray Crystal Structures that Guide the Interpretation of Mutagenesis Studies. Biochemistry. 2019 Jan 14. doi: 10.1021/acs.biochem.8b01103. PMID:30640445 doi:http://dx.doi.org/10.1021/acs.biochem.8b01103
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