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| | ==Crystal structure of the N-terminal domain of sucrase-isomaltase== | | ==Crystal structure of the N-terminal domain of sucrase-isomaltase== |
| - | <StructureSection load='3lpo' size='340' side='right' caption='[[3lpo]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='3lpo' size='340' side='right'caption='[[3lpo]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lpo]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LPO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LPO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lpo]] is a 4 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=3LPO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LPO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 3.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lpp|3lpp]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3lpo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lpo OCA], [https://pdbe.org/3lpo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lpo RCSB], [https://www.ebi.ac.uk/pdbsum/3lpo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lpo 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/Oligo-1,6-glucosidase Oligo-1,6-glucosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.10 3.2.1.10] </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=3lpo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lpo OCA], [http://pdbe.org/3lpo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lpo RCSB], [http://www.ebi.ac.uk/pdbsum/3lpo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lpo ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/SUIS_HUMAN SUIS_HUMAN]] Congenital sucrase-isomaltase deficiency. Defects in SI are the cause of congenital sucrase-isomaltase deficiency (CSID) [MIM:[http://omim.org/entry/222900 222900]]; also known as disaccharide intolerance I. CSID is an autosomal recessive intestinal disorder that is clinically characterized by fermentative diarrhea, abdominal pain, and cramps upon ingestion of sugar. The symptoms are the consequence of absent or drastically reduced enzymatic activities of sucrase and isomaltase. The prevalence of CSID is 0.02 % in individuals of European descent and appears to be much higher in Greenland, Alaskan, and Canadian native people. CSID arises due to post-translational perturbations in the intracellular transport, polarized sorting, aberrant processing, and defective function of SI.<ref>PMID:8609217</ref> <ref>PMID:10903344</ref> <ref>PMID:11340066</ref> <ref>PMID:14724820</ref> <ref>PMID:16329100</ref> | + | [https://www.uniprot.org/uniprot/SUIS_HUMAN SUIS_HUMAN] Congenital sucrase-isomaltase deficiency. Defects in SI are the cause of congenital sucrase-isomaltase deficiency (CSID) [MIM:[https://omim.org/entry/222900 222900]; also known as disaccharide intolerance I. CSID is an autosomal recessive intestinal disorder that is clinically characterized by fermentative diarrhea, abdominal pain, and cramps upon ingestion of sugar. The symptoms are the consequence of absent or drastically reduced enzymatic activities of sucrase and isomaltase. The prevalence of CSID is 0.02 % in individuals of European descent and appears to be much higher in Greenland, Alaskan, and Canadian native people. CSID arises due to post-translational perturbations in the intracellular transport, polarized sorting, aberrant processing, and defective function of SI.<ref>PMID:8609217</ref> <ref>PMID:10903344</ref> <ref>PMID:11340066</ref> <ref>PMID:14724820</ref> <ref>PMID:16329100</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SUIS_HUMAN SUIS_HUMAN]] Plays an important role in the final stage of carbohydrate digestion. Isomaltase activity is specific for both alpha-1,4- and alpha-1,6-oligosaccharides.<ref>PMID:20356844</ref> | + | [https://www.uniprot.org/uniprot/SUIS_HUMAN SUIS_HUMAN] Plays an important role in the final stage of carbohydrate digestion. Isomaltase activity is specific for both alpha-1,4- and alpha-1,6-oligosaccharides.<ref>PMID:20356844</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lp/3lpo_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lp/3lpo_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3lpo" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3lpo" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Alpha-glucosidase 3D structures|Alpha-glucosidase 3D structures]] |
| | + | *[[Sucrase-isomaltase|Sucrase-isomaltase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Oligo-1,6-glucosidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Rose, D R]] | + | [[Category: Rose DR]] |
| - | [[Category: Sim, L]] | + | [[Category: Sim L]] |
| - | [[Category: Alpha-glucosidase]]
| + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Glycosidase]]
| + | |
| - | [[Category: Glycoside hydrolase family 31]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Isomaltase]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Multifunctional enzyme]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Signal-anchor]]
| + | |
| - | [[Category: Sulfation]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
Disease
SUIS_HUMAN Congenital sucrase-isomaltase deficiency. Defects in SI are the cause of congenital sucrase-isomaltase deficiency (CSID) [MIM:222900; also known as disaccharide intolerance I. CSID is an autosomal recessive intestinal disorder that is clinically characterized by fermentative diarrhea, abdominal pain, and cramps upon ingestion of sugar. The symptoms are the consequence of absent or drastically reduced enzymatic activities of sucrase and isomaltase. The prevalence of CSID is 0.02 % in individuals of European descent and appears to be much higher in Greenland, Alaskan, and Canadian native people. CSID arises due to post-translational perturbations in the intracellular transport, polarized sorting, aberrant processing, and defective function of SI.[1] [2] [3] [4] [5]
Function
SUIS_HUMAN Plays an important role in the final stage of carbohydrate digestion. Isomaltase activity is specific for both alpha-1,4- and alpha-1,6-oligosaccharides.[6]
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
Human maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) are small intestinal enzymes that work concurrently to hydrolyze the mixture of linear alpha-1,4- and branched alpha-1,6-oligosaccharide substrates that typically make up terminal starch digestion products. MGAM and SI are each composed of duplicated catalytic domains, N- and C-terminal, which display overlapping substrate specificities. The N-terminal catalytic domain of human MGAM (ntMGAM) has a preference for short linear alpha-1,4-oligosaccharides, whereas N-terminal SI (ntSI) has a broader specificity for both alpha-1,4- and alpha-1,6-oligosaccharides. Here we present the crystal structure of the human ntSI, in apo form to 3.2 A and in complex with the inhibitor kotalanol to 2.15 A resolution. Structural comparison with the previously solved structure of ntMGAM reveals key active site differences in ntSI, including a narrow hydrophobic +1 subsite, which may account for its additional substrate specificity for alpha-1,6 substrates.
Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains.,Sim L, Willemsma C, Mohan S, Naim HY, Pinto BM, Rose DR J Biol Chem. 2010 Jun 4;285(23):17763-70. Epub 2010 Mar 31. PMID:20356844[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ouwendijk J, Moolenaar CE, Peters WJ, Hollenberg CP, Ginsel LA, Fransen JA, Naim HY. Congenital sucrase-isomaltase deficiency. Identification of a glutamine to proline substitution that leads to a transport block of sucrase-isomaltase in a pre-Golgi compartment. J Clin Invest. 1996 Feb 1;97(3):633-41. PMID:8609217 doi:http://dx.doi.org/10.1172/JCI118459
- ↑ Jacob R, Zimmer KP, Schmitz J, Naim HY. Congenital sucrase-isomaltase deficiency arising from cleavage and secretion of a mutant form of the enzyme. J Clin Invest. 2000 Jul;106(2):281-7. PMID:10903344 doi:10.1172/JCI9677
- ↑ Spodsberg N, Jacob R, Alfalah M, Zimmer KP, Naim HY. Molecular basis of aberrant apical protein transport in an intestinal enzyme disorder. J Biol Chem. 2001 Jun 29;276(26):23506-10. Epub 2001 May 4. PMID:11340066 doi:10.1074/jbc.C100219200
- ↑ Ritz V, Alfalah M, Zimmer KP, Schmitz J, Jacob R, Naim HY. Congenital sucrase-isomaltase deficiency because of an accumulation of the mutant enzyme in the endoplasmic reticulum. Gastroenterology. 2003 Dec;125(6):1678-85. PMID:14724820
- ↑ Sander P, Alfalah M, Keiser M, Korponay-Szabo I, Kovacs JB, Leeb T, Naim HY. Novel mutations in the human sucrase-isomaltase gene (SI) that cause congenital carbohydrate malabsorption. Hum Mutat. 2006 Jan;27(1):119. PMID:16329100 doi:10.1002/humu.9392
- ↑ Sim L, Willemsma C, Mohan S, Naim HY, Pinto BM, Rose DR. Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains. J Biol Chem. 2010 Jun 4;285(23):17763-70. Epub 2010 Mar 31. PMID:20356844 doi:10.1074/jbc.M109.078980
- ↑ Sim L, Willemsma C, Mohan S, Naim HY, Pinto BM, Rose DR. Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains. J Biol Chem. 2010 Jun 4;285(23):17763-70. Epub 2010 Mar 31. PMID:20356844 doi:10.1074/jbc.M109.078980
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