4aa2: Difference between revisions
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[[ | ==Crystal structure of ANCE in complex with bradykinin potentiating peptide b== | ||
<StructureSection load='4aa2' size='340' side='right' caption='[[4aa2]], [[Resolution|resolution]] 1.99Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4aa2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AA2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AA2 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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2x94|2x94]], [[1j38|1j38]], [[2x8z|2x8z]], [[1j36|1j36]], [[2xhm|2xhm]], [[2x8y|2x8y]], [[2x91|2x91]], [[2x95|2x95]], [[2x96|2x96]], [[2x92|2x92]], [[2x97|2x97]], [[2x93|2x93]], [[3zqz|3zqz]], [[2x90|2x90]], [[1j37|1j37]], [[4aa1|4aa1]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidyl-dipeptidase_A Peptidyl-dipeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.15.1 3.4.15.1] </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=4aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aa2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4aa2 RCSB], [http://www.ebi.ac.uk/pdbsum/4aa2 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human somatic angiotensin-1 converting enzyme (ACE) is a zinc-dependent exopeptidase, that catalyses the conversion of the decapeptide angiotensin I to the octapeptide angiotensin II, by removing a C-terminal dipeptide. It is the principal component of the renin-angiotensin-aldosterone system that regulates blood pressure. Hence it is an important therapeutic target for the treatment of hypertension and cardiovascular disorders. Here, we report the structures of an ACE homologue from Drosophila melanogaster (AnCE; a proven structural model for the more complex human ACE) co-crystallized with mammalian peptide substrates (bradykinin, Thr(6) -bradykinin, angiotensin I and a snake venom peptide inhibitor, bradykinin-potentiating peptide-b). The structures determined at 2-A resolution illustrate that both angiotensin II (the cleaved product of angiotensin I by AnCE) and bradykinin-potentiating peptide-b bind in an analogous fashion at the active site of AnCE, but also exhibit significant differences. In addition, the binding of Arg-Pro-Pro, the cleavage product of bradykinin and Thr(6) - bradykinin, provides additional detail of the general peptide binding in AnCE. Thus the new structures of AnCE complexes presented here improves our understanding of the binding of peptides and the mechanism by which peptides inhibit this family of enzymes. DATABASE: The atomic coordinates and structure factors for AnCE-Ang II (code 4AA1), AnCE-BPPb (code 4AA2), AnCE-BK (code 4ASQ) and AnCE-Thr6-BK (code 4ASR) complexes have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/) STRUCTURED DIGITAL ABSTRACT: * AnCE cleaves Ang I by enzymatic study (View interaction) * Bradykinin and AnCE bind by x-ray crystallography (View interaction) * BPP and AnCE bind by x-ray crystallography (View interaction) * AnCE cleaves Bradykinin by enzymatic study (View interaction) * Ang II and AnCE bind by x-ray crystallography (View interaction). | |||
Structural basis of peptide recognition by the angiotensin-1 converting enzyme homologue AnCE from Drosophila melanogaster.,Akif M, Masuyer G, Bingham RJ, Sturrock ED, Isaac RE, Acharya KR FEBS J. 2012 Oct 20. doi: 10.1111/febs.12038. PMID:23082758<ref>PMID:23082758</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | |||
*[[Angiotensin-Converting Enzyme|Angiotensin-Converting Enzyme]] | |||
== | == References == | ||
[[ | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Drosophila melanogaster]] | [[Category: Drosophila melanogaster]] | ||
[[Category: Peptidyl-dipeptidase A]] | [[Category: Peptidyl-dipeptidase A]] | ||
[[Category: Acharya, K R | [[Category: Acharya, K R]] | ||
[[Category: Akif, M | [[Category: Akif, M]] | ||
[[Category: Isaac, R E | [[Category: Isaac, R E]] | ||
[[Category: Masuyer, G | [[Category: Masuyer, G]] | ||
[[Category: Schwager, S L.U | [[Category: Schwager, S L.U]] | ||
[[Category: Sturrock, E D | [[Category: Sturrock, E D]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Hydrolase-peptide complex]] | [[Category: Hydrolase-peptide complex]] | ||
[[Category: Inhibitor]] | [[Category: Inhibitor]] | ||
[[Category: Substrate binding]] | [[Category: Substrate binding]] | ||
Revision as of 19:46, 9 December 2014
Crystal structure of ANCE in complex with bradykinin potentiating peptide bCrystal structure of ANCE in complex with bradykinin potentiating peptide b
Structural highlights
Publication Abstract from PubMedHuman somatic angiotensin-1 converting enzyme (ACE) is a zinc-dependent exopeptidase, that catalyses the conversion of the decapeptide angiotensin I to the octapeptide angiotensin II, by removing a C-terminal dipeptide. It is the principal component of the renin-angiotensin-aldosterone system that regulates blood pressure. Hence it is an important therapeutic target for the treatment of hypertension and cardiovascular disorders. Here, we report the structures of an ACE homologue from Drosophila melanogaster (AnCE; a proven structural model for the more complex human ACE) co-crystallized with mammalian peptide substrates (bradykinin, Thr(6) -bradykinin, angiotensin I and a snake venom peptide inhibitor, bradykinin-potentiating peptide-b). The structures determined at 2-A resolution illustrate that both angiotensin II (the cleaved product of angiotensin I by AnCE) and bradykinin-potentiating peptide-b bind in an analogous fashion at the active site of AnCE, but also exhibit significant differences. In addition, the binding of Arg-Pro-Pro, the cleavage product of bradykinin and Thr(6) - bradykinin, provides additional detail of the general peptide binding in AnCE. Thus the new structures of AnCE complexes presented here improves our understanding of the binding of peptides and the mechanism by which peptides inhibit this family of enzymes. DATABASE: The atomic coordinates and structure factors for AnCE-Ang II (code 4AA1), AnCE-BPPb (code 4AA2), AnCE-BK (code 4ASQ) and AnCE-Thr6-BK (code 4ASR) complexes have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/) STRUCTURED DIGITAL ABSTRACT: * AnCE cleaves Ang I by enzymatic study (View interaction) * Bradykinin and AnCE bind by x-ray crystallography (View interaction) * BPP and AnCE bind by x-ray crystallography (View interaction) * AnCE cleaves Bradykinin by enzymatic study (View interaction) * Ang II and AnCE bind by x-ray crystallography (View interaction). Structural basis of peptide recognition by the angiotensin-1 converting enzyme homologue AnCE from Drosophila melanogaster.,Akif M, Masuyer G, Bingham RJ, Sturrock ED, Isaac RE, Acharya KR FEBS J. 2012 Oct 20. doi: 10.1111/febs.12038. PMID:23082758[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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