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[[Image:3ole.png|left|200px]]


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==Structures of human pancreatic alpha-amylase in complex with acarviostatin II03==
The line below this paragraph, containing "STRUCTURE_3ole", creates the "Structure Box" on the page.
<StructureSection load='3ole' size='340' side='right'caption='[[3ole]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[3ole]] is a 1 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=3OLE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OLE FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACI:6-AMINO-4-HYDROXYMETHYL-CYCLOHEX-4-ENE-1,2,3-TRIOL'>ACI</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G6D:6-DEOXY-ALPHA-D-GLUCOSE'>G6D</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=PRD_900009:alpha-maltotriose'>PRD_900009</scene>, <scene name='pdbligand=PRD_900065:beta-maltotriose'>PRD_900065</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
{{STRUCTURE_3ole|  PDB=3ole  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ole FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ole OCA], [https://pdbe.org/3ole PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ole RCSB], [https://www.ebi.ac.uk/pdbsum/3ole PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ole ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AMYP_HUMAN AMYP_HUMAN]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human pancreatic alpha-amylase (HPA) catalyzes the hydrolysis of alpha-d-(1,4) glycosidic linkages in starch and is one of the major therapeutic targets for type II diabetes. Several acarviostatins isolated from Streptomyces coelicoflavus var. nankaiensis previously showed more potent inhibition of HPA than acarbose, which has been successfully used in clinical therapy. However, the molecular mechanisms by which acarviostatins inhibit HPA remains elusive. Here we determined crystal structures of HPA in complexes with a series of acarviostatin inhibitors (I03, II03, III03, and IV03). Structural analyses showed that acarviostatin I03 undergoes a series of hydrolysis and condensation reactions in the HPA active site, similar to acarbose, while acarviostatins II03, III03, and IV03 likely undergo only hydrolysis reactions. On the basis of structural analysis combined with kinetic assays, we demonstrate that the final modified product with seven sugar rings is best suited for occupying the full active site and shows the most efficient inhibition of HPA. Our high resolution structures reported here identify first time an interaction between an inhibitor and subsite-4 of the HPA active site, which we show makes a significant contribution to the inhibitory effect. Our results provide important information for the design of new drugs for the treatment of type II diabetes or obesity.


===Structures of human pancreatic alpha-amylase in complex with acarviostatin II03===
Structures of human pancreatic alpha-amylase in complex with acarviostatins: Implications for drug design against type II diabetes.,Qin X, Ren L, Yang X, Bai F, Wang L, Geng P, Bai G, Shen Y J Struct Biol. 2011 Apr;174(1):196-202. Epub 2010 Nov 24. PMID:21111049<ref>PMID:21111049</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3ole" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_21111049}}, adds the Publication Abstract to the page
*[[Amylase 3D structures|Amylase 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 21111049 is the PubMed ID number.
== References ==
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<references/>
{{ABSTRACT_PUBMED_21111049}}
__TOC__
 
</StructureSection>
==About this Structure==
[[3ole]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OLE OCA].
 
==Reference==
<ref group="xtra">PMID:21111049</ref><references group="xtra"/>
[[Category: Alpha-amylase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Qin, X.]]
[[Category: Large Structures]]
[[Category: Ren, L.]]
[[Category: Qin X]]
[[Category: Ren L]]

Latest revision as of 19:55, 1 November 2023

Structures of human pancreatic alpha-amylase in complex with acarviostatin II03Structures of human pancreatic alpha-amylase in complex with acarviostatin II03

Structural highlights

3ole is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.55Å
Ligands:, , , , , , , , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AMYP_HUMAN

Publication Abstract from PubMed

Human pancreatic alpha-amylase (HPA) catalyzes the hydrolysis of alpha-d-(1,4) glycosidic linkages in starch and is one of the major therapeutic targets for type II diabetes. Several acarviostatins isolated from Streptomyces coelicoflavus var. nankaiensis previously showed more potent inhibition of HPA than acarbose, which has been successfully used in clinical therapy. However, the molecular mechanisms by which acarviostatins inhibit HPA remains elusive. Here we determined crystal structures of HPA in complexes with a series of acarviostatin inhibitors (I03, II03, III03, and IV03). Structural analyses showed that acarviostatin I03 undergoes a series of hydrolysis and condensation reactions in the HPA active site, similar to acarbose, while acarviostatins II03, III03, and IV03 likely undergo only hydrolysis reactions. On the basis of structural analysis combined with kinetic assays, we demonstrate that the final modified product with seven sugar rings is best suited for occupying the full active site and shows the most efficient inhibition of HPA. Our high resolution structures reported here identify first time an interaction between an inhibitor and subsite-4 of the HPA active site, which we show makes a significant contribution to the inhibitory effect. Our results provide important information for the design of new drugs for the treatment of type II diabetes or obesity.

Structures of human pancreatic alpha-amylase in complex with acarviostatins: Implications for drug design against type II diabetes.,Qin X, Ren L, Yang X, Bai F, Wang L, Geng P, Bai G, Shen Y J Struct Biol. 2011 Apr;174(1):196-202. Epub 2010 Nov 24. PMID:21111049[1]

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

See Also

References

  1. ↑ Qin X, Ren L, Yang X, Bai F, Wang L, Geng P, Bai G, Shen Y. Structures of human pancreatic alpha-amylase in complex with acarviostatins: Implications for drug design against type II diabetes. J Struct Biol. 2011 Apr;174(1):196-202. Epub 2010 Nov 24. PMID:21111049 doi:10.1016/j.jsb.2010.11.020

3ole, resolution 1.55Å

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