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1u8f

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Revision as of 08:46, 21 March 2018

Crystal Structure Of Human Placental Glyceraldehyde-3-Phosphate Dehydrogenase At 1.75 Resolution

Structural highlights

1u8f is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3gpd
Gene:	GAPD (HUMAN)
Activity:	Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating), with EC number 1.2.1.12
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[G3P_HUMAN] Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.^[1] ^[2] ^[3]

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

GAPDH (D-glyceraldehyde-3-phosphate dehydrogenase) is a multifunctional protein that is a target for the design of antitrypanosomatid and anti-apoptosis drugs. Here, the first high-resolution (1.75 Angstroms) structure of a human GAPDH is reported. The structure shows that the intersubunit selectivity cleft that has been leveraged in the design of antitrypanosomatid compounds is closed in human GAPDH. Modeling of an anti-trypanosomatid GAPDH inhibitor in the human GAPDH active site provides insights into the basis for the observed selectivity of this class of inhibitor. Moreover, the high-resolution data reveal a new feature of the cleft: water-mediated intersubunit hydrogen bonds that assist closure of the cleft in the human enzyme. The structure is used in a computational ligand-docking study of the small-molecule compound CGP-3466, which inhibits apoptosis by preventing nuclear accumulation of GAPDH. Plausible binding sites are identified in the adenosine pocket of the NAD(+)-binding site and in a hydrophobic channel located in the center of the tetramer near the intersection of the three molecular twofold axes. The structure is also used to build a qualitative model of the complex between GAPDH and the E3 ubiquitin ligase Siah1. The model suggests that the convex surface near GAPDH Lys227 interacts with a large shallow groove of the Siah1 dimer. These results are discussed in the context of the recently discovered NO-S-nitrosylation-GAPDH-Siah1 apoptosis cascade.

High-resolution structure of human D-glyceraldehyde-3-phosphate dehydrogenase.,Jenkins JL, Tanner JJ Acta Crystallogr D Biol Crystallogr. 2006 Mar;62(Pt 3):290-301. Epub 2006, Feb 22. PMID:16510976^[4]

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

References

↑ Ercolani L, Florence B, Denaro M, Alexander M. Isolation and complete sequence of a functional human glyceraldehyde-3-phosphate dehydrogenase gene. J Biol Chem. 1988 Oct 25;263(30):15335-41. PMID:3170585
↑ Tisdale EJ. Glyceraldehyde-3-phosphate dehydrogenase is phosphorylated by protein kinase Ciota /lambda and plays a role in microtubule dynamics in the early secretory pathway. J Biol Chem. 2002 Feb 1;277(5):3334-41. Epub 2001 Nov 27. PMID:11724794 doi:10.1074/jbc.M109744200
↑ Arif A, Chatterjee P, Moodt RA, Fox PL. Heterotrimeric GAIT complex drives transcript-selective translation inhibition in murine macrophages. Mol Cell Biol. 2012 Dec;32(24):5046-55. doi: 10.1128/MCB.01168-12. Epub 2012 Oct , 15. PMID:23071094 doi:10.1128/MCB.01168-12
↑ Jenkins JL, Tanner JJ. High-resolution structure of human D-glyceraldehyde-3-phosphate dehydrogenase. Acta Crystallogr D Biol Crystallogr. 2006 Mar;62(Pt 3):290-301. Epub 2006, Feb 22. PMID:16510976 doi:10.1107/S0907444905042289

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://52.214.119.220/wiki/index.php/1u8f"

@@ Line 1: / Line 1: @@
 ==Crystal Structure Of Human Placental Glyceraldehyde-3-Phosphate Dehydrogenase At 1.75 Resolution==
 <StructureSection load='1u8f' size='340' side='right' caption='[[1u8f]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GAPD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u8f OCA], [http://pdbe.org/1u8f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u8f RCSB], [http://www.ebi.ac.uk/pdbsum/1u8f PDBsum]</span></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=1u8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u8f OCA], [http://pdbe.org/1u8f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u8f RCSB], [http://www.ebi.ac.uk/pdbsum/1u8f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1u8f ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u8/1u8f_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u8/1u8f_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1u8f

From Proteopedia

Revision as of 08:46, 21 March 2018

Crystal Structure Of Human Placental Glyceraldehyde-3-Phosphate Dehydrogenase At 1.75 Resolution

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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