1dhk
From Proteopedia
(New page: 200px<br /><applet load="1dhk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dhk, resolution 1.85Å" /> '''STRUCTURE OF PORCINE...) |
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| - | [[Image:1dhk.gif|left|200px]]<br /><applet load="1dhk" size=" | + | [[Image:1dhk.gif|left|200px]]<br /><applet load="1dhk" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1dhk, resolution 1.85Å" /> | caption="1dhk, resolution 1.85Å" /> | ||
'''STRUCTURE OF PORCINE PANCREATIC ALPHA-AMYLASE'''<br /> | '''STRUCTURE OF PORCINE PANCREATIC ALPHA-AMYLASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: alpha-Amylases catalyze the hydrolysis of glycosidic linkages | + | BACKGROUND: alpha-Amylases catalyze the hydrolysis of glycosidic linkages in starch and other related polysaccharides. The alpha-amylase inhibitor (alpha-Al) from the bean Phaseolus vulgaris belongs to a family of plant defence proteins and is a potent inhibitor of mammalian alpha-amylases. The structure of pig pancreatic alpha-amylase (PPA) in complex with both a carbohydrate inhibitor (acarbose) and a proteinaceous inhibitor (Tendamistat) is known, but the catalytic mechanism is poorly understood. RESULTS: The crystal structure of pig pancreatic alpha-amylase complexed with alpha-Al was refined to 1.85 A resolution. It reveals that in complex with PPA, the inhibitor has the typical dimer structure common to legume lectins. Two hairpin loops extending out from the jellyroll fold of a monomer interact directly with the active site region of the enzyme molecule, with the inhibitor molecule filling the whole substrate-docking region of the PPA. The inhibitor makes substrate-mimetic interactions with binding subsites of the enzyme and targets catalytic residues in the active site. Binding of inhibitor induces structural changes at the active site of the enzyme. CONCLUSIONS: The present analysis reveals that there are extensive interactions between the inhibitor and residues that are highly conserved in the active site of alpha-amylases; alpha-Al1 inactivates PPA through elaborate blockage of substrate-binding sites. It provides a basis to design peptide analogue inhibitors. alpha-Amylase inhibition is of interest from several points of view, for example the treatment of diabetes and for crop protection. |
==About this Structure== | ==About this Structure== | ||
| - | 1DHK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Phaseolus_vulgaris Phaseolus vulgaris] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with NAG, CA and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1DHK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Phaseolus_vulgaris Phaseolus vulgaris] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DHK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: porcine]] | [[Category: porcine]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:16:37 2008'' |
Revision as of 10:16, 21 February 2008
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STRUCTURE OF PORCINE PANCREATIC ALPHA-AMYLASE
Overview
BACKGROUND: alpha-Amylases catalyze the hydrolysis of glycosidic linkages in starch and other related polysaccharides. The alpha-amylase inhibitor (alpha-Al) from the bean Phaseolus vulgaris belongs to a family of plant defence proteins and is a potent inhibitor of mammalian alpha-amylases. The structure of pig pancreatic alpha-amylase (PPA) in complex with both a carbohydrate inhibitor (acarbose) and a proteinaceous inhibitor (Tendamistat) is known, but the catalytic mechanism is poorly understood. RESULTS: The crystal structure of pig pancreatic alpha-amylase complexed with alpha-Al was refined to 1.85 A resolution. It reveals that in complex with PPA, the inhibitor has the typical dimer structure common to legume lectins. Two hairpin loops extending out from the jellyroll fold of a monomer interact directly with the active site region of the enzyme molecule, with the inhibitor molecule filling the whole substrate-docking region of the PPA. The inhibitor makes substrate-mimetic interactions with binding subsites of the enzyme and targets catalytic residues in the active site. Binding of inhibitor induces structural changes at the active site of the enzyme. CONCLUSIONS: The present analysis reveals that there are extensive interactions between the inhibitor and residues that are highly conserved in the active site of alpha-amylases; alpha-Al1 inactivates PPA through elaborate blockage of substrate-binding sites. It provides a basis to design peptide analogue inhibitors. alpha-Amylase inhibition is of interest from several points of view, for example the treatment of diabetes and for crop protection.
About this Structure
1DHK is a Protein complex structure of sequences from Phaseolus vulgaris and Sus scrofa with , and as ligands. Active as Alpha-amylase, with EC number 3.2.1.1 Full crystallographic information is available from OCA.
Reference
Substrate mimicry in the active center of a mammalian alpha-amylase: structural analysis of an enzyme-inhibitor complex., Bompard-Gilles C, Rousseau P, Rouge P, Payan F, Structure. 1996 Dec 15;4(12):1441-52. PMID:8994970
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