|
|
| (18 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:4ald.gif|left|200px]]<br /><applet load="4ald" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="4ald, resolution 2.8Å" /> | |
| - | '''HUMAN MUSCLE FRUCTOSE 1,6-BISPHOSPHATE ALDOLASE COMPLEXED WITH FRUCTOSE 1,6-BISPHOSPHATE'''<br /> | |
| | | | |
| - | ==Overview== | + | ==HUMAN MUSCLE FRUCTOSE 1,6-BISPHOSPHATE ALDOLASE COMPLEXED WITH FRUCTOSE 1,6-BISPHOSPHATE== |
| - | Fructose 1,6-bisphosphate aldolase catalyzes the reversible cleavage of fructose 1,6-bisphosphate and fructose 1-phosphate to dihydroxyacetone phosphate and either glyceraldehyde 3-phosphate or glyceraldehyde, respectively. Catalysis involves the formation of a Schiff's base intermediate formed at the epsilon-amino group of Lys229. The existing apo-enzyme structure was refined using the crystallographic free-R-factor and maximum likelihood methods that have been shown to give improved structural results that are less subject to model bias. Crystals were also soaked with the natural substrate (fructose 1,6-bisphosphate), and the crystal structure of this complex has been determined to 2.8 A. The apo structure differs from the previous Brookhaven-deposited structure (1ald) in the flexible C-terminal region. This is also the region where the native and complex structures exhibit differences. The conformational changes between native and complex structure are not large, but the observed complex does not involve the full formation of the Schiff's base intermediate, and suggests a preliminary hydrogen-bonded Michaelis complex before the formation of the covalent complex.
| + | <StructureSection load='4ald' size='340' side='right'caption='[[4ald]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[4ald]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The February 2004 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''The Glycolytic Enzymes'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2004_2 10.2210/rcsb_pdb/mom_2004_2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ALD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ALD 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]] 2.8Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2FP:1,6-FRUCTOSE+DIPHOSPHATE+(LINEAR+FORM)'>2FP</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=4ald FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ald OCA], [https://pdbe.org/4ald PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ald RCSB], [https://www.ebi.ac.uk/pdbsum/4ald PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ald ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/ALDOA_HUMAN ALDOA_HUMAN] Defects in ALDOA are the cause of glycogen storage disease type 12 (GSD12) [MIM:[https://omim.org/entry/611881 611881]; also known as red cell aldolase deficiency. A metabolic disorder associated with increased hepatic glycogen and hemolytic anemia. It may lead to myopathy with exercise intolerance and rhabdomyolysis.<ref>PMID:14766013</ref> <ref>PMID:2825199</ref> <ref>PMID:2229018</ref> <ref>PMID:8598869</ref> <ref>PMID:14615364</ref> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/ALDOA_HUMAN ALDOA_HUMAN] Plays a key role in glycolysis and gluconeogenesis. In addition, may also function as scaffolding protein (By similarity). |
| | + | == 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/al/4ald_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=4ald ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | ==Disease== | + | ==See Also== |
| - | Known disease associated with this structure: Aldolase A deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=103850 103850]]
| + | *[[Aldolase|Aldolase]] |
| - | | + | *[[Aldolase 3D structures|Aldolase 3D structures]] |
| - | ==About this Structure==
| + | == References == |
| - | 4ALD 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 <scene name='pdbligand=2FP:'>2FP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. The following page contains interesting information on the relation of 4ALD with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb50_1.html The Glycolytic Enzymes]]. Active as [http://en.wikipedia.org/wiki/Fructose-bisphosphate_aldolase Fructose-bisphosphate aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.13 4.1.2.13] Known structural/functional Site: <scene name='pdbsite=SBL:Schiff'S+Base+LYS'>SBL</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ALD OCA].
| + | <references/> |
| - | | + | __TOC__ |
| - | ==Reference==
| + | </StructureSection> |
| - | Crystal structure of human muscle aldolase complexed with fructose 1,6-bisphosphate: mechanistic implications., Dalby A, Dauter Z, Littlechild JA, Protein Sci. 1999 Feb;8(2):291-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10048322 10048322]
| + | |
| - | [[Category: Fructose-bisphosphate aldolase]]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| | + | [[Category: RCSB PDB Molecule of the Month]] |
| | [[Category: The Glycolytic Enzymes]] | | [[Category: The Glycolytic Enzymes]] |
| - | [[Category: Dalby, A R.]] | + | [[Category: Dalby AR]] |
| - | [[Category: Dauter, Z.]] | + | [[Category: Dauter Z]] |
| - | [[Category: Littlechild, J A.]] | + | [[Category: Littlechild JA]] |
| - | [[Category: 2FP]]
| + | |
| - | [[Category: complex]]
| + | |
| - | [[Category: lyase (aldehyde)]]
| + | |
| - | [[Category: tim barrel]]
| + | |
| - | [[Category: type 1 aldolase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:12:42 2008''
| + | |
| Structural highlights
Disease
ALDOA_HUMAN Defects in ALDOA are the cause of glycogen storage disease type 12 (GSD12) [MIM:611881; also known as red cell aldolase deficiency. A metabolic disorder associated with increased hepatic glycogen and hemolytic anemia. It may lead to myopathy with exercise intolerance and rhabdomyolysis.[1] [2] [3] [4] [5]
Function
ALDOA_HUMAN Plays a key role in glycolysis and gluconeogenesis. In addition, may also function as scaffolding protein (By similarity).
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
- ↑ Esposito G, Vitagliano L, Costanzo P, Borrelli L, Barone R, Pavone L, Izzo P, Zagari A, Salvatore F. Human aldolase A natural mutants: relationship between flexibility of the C-terminal region and enzyme function. Biochem J. 2004 May 15;380(Pt 1):51-6. PMID:14766013 doi:10.1042/BJ20031941
- ↑ Kishi H, Mukai T, Hirono A, Fujii H, Miwa S, Hori K. Human aldolase A deficiency associated with a hemolytic anemia: thermolabile aldolase due to a single base mutation. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8623-7. PMID:2825199
- ↑ Takasaki Y, Takahashi I, Mukai T, Hori K. Human aldolase A of a hemolytic anemia patient with Asp-128----Gly substitution: characteristics of an enzyme generated in E. coli transfected with the expression plasmid pHAAD128G. J Biochem. 1990 Aug;108(2):153-7. PMID:2229018
- ↑ Kreuder J, Borkhardt A, Repp R, Pekrun A, Gottsche B, Gottschalk U, Reichmann H, Schachenmayr W, Schlegel K, Lampert F. Brief report: inherited metabolic myopathy and hemolysis due to a mutation in aldolase A. N Engl J Med. 1996 Apr 25;334(17):1100-4. PMID:8598869 doi:http://dx.doi.org/10.1056/NEJM199604253341705
- ↑ Yao DC, Tolan DR, Murray MF, Harris DJ, Darras BT, Geva A, Neufeld EJ. Hemolytic anemia and severe rhabdomyolysis caused by compound heterozygous mutations of the gene for erythrocyte/muscle isozyme of aldolase, ALDOA(Arg303X/Cys338Tyr). Blood. 2004 Mar 15;103(6):2401-3. Epub 2003 Nov 13. PMID:14615364 doi:10.1182/blood-2003-09-3160
|
