3bai: Difference between revisions

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-[[Image:3bai.jpg|left|200px]]
- {{Structure
+==Human Pancreatic Alpha Amylase with Bound Nitrate==
-|PDB= 3bai |SIZE=350|CAPTION= <scene name='initialview01'>3bai</scene>, resolution 1.9&Aring;
+<StructureSection load='3bai' size='340' side='right'caption='[[3bai]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
-|SITE= <scene name='pdbsite=AC1:Nag+Binding+Site+For+Residue+A+497'>AC1</scene>, <scene name='pdbsite=AC2:No3+Binding+Site+For+Residue+A+500'>AC2</scene> and <scene name='pdbsite=AC3:Ca+Binding+Site+For+Residue+A+498'>AC3</scene>
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>
+<table><tr><td colspan='2'>[[3bai]] 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=3BAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BAI FirstGlance]. <br>
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Alpha-amylase Alpha-amylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.1 3.2.1.1] </span>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
-|GENE= AMY2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
-|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam00128 Alpha-amylase], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=smart00632 Aamy_C]</span>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bai OCA], [https://pdbe.org/3bai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bai RCSB], [https://www.ebi.ac.uk/pdbsum/3bai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bai ProSAT]</span></td></tr>
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bai OCA], [http://www.ebi.ac.uk/pdbsum/3bai PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=3bai RCSB]</span>
+</table>
-}}
+== Function ==
+[https://www.uniprot.org/uniprot/AMYP_HUMAN AMYP_HUMAN]
+== 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/ba/3bai_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=3bai ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A mechanistic study of the essential allosteric activation of human pancreatic alpha-amylase by chloride ion has been conducted by exploring a wide range of anion substitutions through kinetic and structural experiments. Surprisingly, kinetic studies indicate that the majority of these alternative anions can induce some level of enzymatic activity despite very different atomic geometries, sizes, and polyatomic natures. These data and subsequent structural studies attest to the remarkable plasticity of the chloride binding site, even though earlier structural studies of wild-type human pancreatic alpha-amylase suggested this site would likely be restricted to chloride binding. Notably, no apparent relationship is observed between anion binding affinity and relative activity, emphasizing the complexity of the relationship between chloride binding parameters and the activation mechanism that facilitates catalysis. Of the anions studied, particularly intriguing in terms of observed trends in substrate kinetics and their novel atomic compositions were the nitrite, nitrate, and azide anions, the latter of which was found to enhance the relative activity of human pancreatic alpha-amylase by nearly 5-fold. Structural studies have provided considerable insight into the nature of the interactions formed in the chloride binding site by the nitrite and nitrate anions. To probe the role such interactions play in allosteric activation, further structural analyses were conducted in the presence of acarbose, which served as a sensitive reporter molecule of the catalytic ability of these modified enzymes to carry out its expected rearrangement by human pancreatic alpha-amylase. These studies show that the largest anion of this group, nitrate, can comfortably fit in the chloride binding pocket, making all the necessary hydrogen bonds. Further, this anion has nearly the same ability to activate human pancreatic alpha-amylase and leads to the production of the same acarbose product. In contrast, while nitrite considerably boosts the relative activity of human pancreatic alpha-amylase, its presence leads to changes in the electrostatic environment and active site conformations that substantially modify catalytic parameters and produce a novel acarbose rearrangement product. In particular, nitrite-substituted human pancreatic alpha-amylase demonstrates the unique ability to cleave acarbose into its acarviosine and maltose parts and carry out a previously unseen product elongation. In a completely unexpected turn of events, structural studies show that in azide-bound human pancreatic alpha-amylase, the normally resident chloride ion is retained in its binding site and an azide anion is found bound in an embedded side pocket in the substrate binding cleft. These results clearly indicate that azide enzymatic activation occurs via a mechanism distinct from that of the nitrite and nitrate anions.
-'''Human Pancreatic Alpha Amylase with Bound Nitrate'''
+Alternative catalytic anions differentially modulate human alpha-amylase activity and specificity(,).,Maurus R, Begum A, Williams LK, Fredriksen JR, Zhang R, Withers SG, Brayer GD Biochemistry. 2008 Mar 18;47(11):3332-44. Epub 2008 Feb 20. PMID:18284212<ref>PMID:18284212</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3bai" style="background-color:#fffaf0;"></div>
-==Overview==
+==See Also==
-A mechanistic study of the essential allosteric activation of human pancreatic alpha-amylase by chloride ion has been conducted by exploring a wide range of anion substitutions through kinetic and structural experiments. Surprisingly, kinetic studies indicate that the majority of these alternative anions can induce some level of enzymatic activity despite very different atomic geometries, sizes, and polyatomic natures. These data and subsequent structural studies attest to the remarkable plasticity of the chloride binding site, even though earlier structural studies of wild-type human pancreatic alpha-amylase suggested this site would likely be restricted to chloride binding. Notably, no apparent relationship is observed between anion binding affinity and relative activity, emphasizing the complexity of the relationship between chloride binding parameters and the activation mechanism that facilitates catalysis. Of the anions studied, particularly intriguing in terms of observed trends in substrate kinetics and their novel atomic compositions were the nitrite, nitrate, and azide anions, the latter of which was found to enhance the relative activity of human pancreatic alpha-amylase by nearly 5-fold. Structural studies have provided considerable insight into the nature of the interactions formed in the chloride binding site by the nitrite and nitrate anions. To probe the role such interactions play in allosteric activation, further structural analyses were conducted in the presence of acarbose, which served as a sensitive reporter molecule of the catalytic ability of these modified enzymes to carry out its expected rearrangement by human pancreatic alpha-amylase. These studies show that the largest anion of this group, nitrate, can comfortably fit in the chloride binding pocket, making all the necessary hydrogen bonds. Further, this anion has nearly the same ability to activate human pancreatic alpha-amylase and leads to the production of the same acarbose product. In contrast, while nitrite considerably boosts the relative activity of human pancreatic alpha-amylase, its presence leads to changes in the electrostatic environment and active site conformations that substantially modify catalytic parameters and produce a novel acarbose rearrangement product. In particular, nitrite-substituted human pancreatic alpha-amylase demonstrates the unique ability to cleave acarbose into its acarviosine and maltose parts and carry out a previously unseen product elongation. In a completely unexpected turn of events, structural studies show that in azide-bound human pancreatic alpha-amylase, the normally resident chloride ion is retained in its binding site and an azide anion is found bound in an embedded side pocket in the substrate binding cleft. These results clearly indicate that azide enzymatic activation occurs via a mechanism distinct from that of the nitrite and nitrate anions.
+*[[Amylase 3D structures|Amylase 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-BAI is a [[Single protein]] structure of 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=3BAI OCA].
+__TOC__
+</StructureSection>
-==Reference==
-Alternative catalytic anions differentially modulate human alpha-amylase activity and specificity(,)., Maurus R, Begum A, Williams LK, Fredriksen JR, Zhang R, Withers SG, Brayer GD, Biochemistry. 2008 Mar 18;47(11):3332-44. Epub 2008 Feb 20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18284212 18284212]
-[[Category: Alpha-amylase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Brayer, G D.]]
+[[Category: Brayer GD]]
-[[Category: Fredriksen, J R.]]
+[[Category: Fredriksen JR]]
-[[Category: Maurus, R.]]
+[[Category: Maurus R]]
-[[Category: anion activation]]
-[[Category: calcium]]
-[[Category: carbohydrate metabolism]]
-[[Category: chloride]]
-[[Category: diabetes]]
-[[Category: enzyme]]
-[[Category: glycoprotein]]
-[[Category: glycosidase]]
-[[Category: human]]
-[[Category: hydrolase]]
-[[Category: metal-binding]]
-[[Category: nitrate]]
-[[Category: pancreatic]]
-[[Category: pyrrolidone carboxylic acid]]
-[[Category: secreted]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 26 09:55:32 2008''