This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3lpp

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Crystal complex of N-terminal sucrase-isomaltase with kotalanol

Structural highlights

3lpp 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:	3lpo
Gene:	SI (HUMAN)
Activity:	Oligo-1,6-glucosidase, with EC number 3.2.1.10
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3lpp"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3lpp]] 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=3LPP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LPP 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KTL:(1S,2R,3R,4S)-1-{(1S)-2-[(2R,3S,4S)-3,4-DIHYDROXY-2-(HYDROXYMETHYL)TETRAHYDROTHIOPHENIUM-1-YL]-1-HYDROXYETHYL}-2,3,4,5-TETRAHYDROXYPENTYL+SULFATE'>KTL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
+</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KTL:(1S,2R,3R,4S)-1-{(1S)-2-[(2R,3S,4S)-3,4-DIHYDROXY-2-(HYDROXYMETHYL)TETRAHYDROTHIOPHENIUM-1-YL]-1-HYDROXYETHYL}-2,3,4,5-TETRAHYDROXYPENTYL+SULFATE'>KTL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lpo|3lpo]]</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>
@@ Line 52: / Line 52: @@
 [[Category: Membrane]]
 [[Category: Multifunctional enzyme]]
+[[Category: Polymorphism]]
 [[Category: Signal-anchor]]
 [[Category: Sulfation]]
 [[Category: Transmembrane]]

3lpp

From Proteopedia

Current revision

Crystal complex of N-terminal sucrase-isomaltase with kotalanol

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox