6bv4

From Proteopedia

(Difference between revisions)

Revision as of 08:32, 10 January 2018

Crystal structure of porcine aminopeptidase-N with Methionine

Structural highlights

6bv4 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Activity:	Membrane alanyl aminopeptidase, with EC number 3.4.11.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[AMPN_PIG] Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May be involved in the metabolism of regulatory peptides of diverse cell types, responsible for the processing of peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines and involved the cleavage of peptides bound to major histocompatibility complex class II molecules of antigen presenting cells. May have a role in angiogenesis (By similarity). It is able to degrade Leu-enkephalin and Met-enkephalin but not cholecystokinin CCK8, neuromedin C (GRP-10), somatostatin-14, substance P and vasoactive intestinal peptide. In case of porcine transmissible gastroenteritis coronavirus (TGEV) and porcine respiratory coronavirus (PRCoV) infections, serves as a receptor for TGEV and PRCoV spike glycoprotein in a species-specific manner.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The M1 family of metalloproteases represents a large number of exopeptidases that cleave single amino acid residues from the N-terminus of peptide substrates. One member of this family that has been well studied is aminopeptidase N (APN), a multifunctional protease known to cleave biologically active peptides and aide in coronavirus entry. The proteolytic activity of APN promotes cancer angiogenesis and metastasis making it an important target for cancer therapy. To understand the substrate specificity of APN for the development of targeted inhibitors, we used a global substrate profiling method to determine the P1-P4' amino acid preferences. The key structural features of the APN pharmacophore required for substrate recognition were elucidated by x-ray crystallography. By combining these substrate profiling and structural data, we were able to design a selective peptide inhibitor of APN that was an effective therapeutic both in vitro and in vivo against APN-expressing prostate cancer models.

The Rational Design of Therapeutic Peptides for Aminopeptidase N using a Substrate-Based Approach.,Joshi S, Chen L, Winter MB, Lin YL, Yang Y, Shapovalova M, Smith PM, Liu C, Li F, LeBeau AM Sci Rep. 2017 May 2;7(1):1424. doi: 10.1038/s41598-017-01542-5. PMID:28465619^[6]

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

References

↑ Delmas B, Gelfi J, Kut E, Sjostrom H, Noren O, Laude H. Determinants essential for the transmissible gastroenteritis virus-receptor interaction reside within a domain of aminopeptidase-N that is distinct from the enzymatic site. J Virol. 1994 Aug;68(8):5216-24. PMID:7913510
↑ Delmas B, Gelfi J, L'Haridon R, Vogel LK, Sjostrom H, Noren O, Laude H. Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV. Nature. 1992 Jun 4;357(6377):417-20. PMID:1350661 doi:http://dx.doi.org/10.1038/357417a0
↑ Delmas B, Gelfi J, Sjostrom H, Noren O, Laude H. Further characterization of aminopeptidase-N as a receptor for coronaviruses. Adv Exp Med Biol. 1993;342:293-8. PMID:7911642
↑ Benbacer L, Kut E, Besnardeau L, Laude H, Delmas B. Interspecies aminopeptidase-N chimeras reveal species-specific receptor recognition by canine coronavirus, feline infectious peritonitis virus, and transmissible gastroenteritis virus. J Virol. 1997 Jan;71(1):734-7. PMID:8985407
↑ Hegyi A, Kolb AF. Characterization of determinants involved in the feline infectious peritonitis virus receptor function of feline aminopeptidase N. J Gen Virol. 1998 Jun;79 ( Pt 6):1387-91. PMID:9634079
↑ Joshi S, Chen L, Winter MB, Lin YL, Yang Y, Shapovalova M, Smith PM, Liu C, Li F, LeBeau AM. The Rational Design of Therapeutic Peptides for Aminopeptidase N using a Substrate-Based Approach. Sci Rep. 2017 May 2;7(1):1424. doi: 10.1038/s41598-017-01542-5. PMID:28465619 doi:http://dx.doi.org/10.1038/s41598-017-01542-5

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6bv4"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6bv4 is ON HOLD
+==Crystal structure of porcine aminopeptidase-N with Methionine==
+<StructureSection load='6bv4' size='340' side='right' caption='[[6bv4]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6bv4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BV4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BV4 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MET:METHIONINE'>MET</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Membrane_alanyl_aminopeptidase Membrane alanyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.2 3.4.11.2] </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=6bv4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bv4 OCA], [http://pdbe.org/6bv4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bv4 RCSB], [http://www.ebi.ac.uk/pdbsum/6bv4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bv4 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/AMPN_PIG AMPN_PIG]] Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May be involved in the metabolism of regulatory peptides of diverse cell types, responsible for the processing of peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines and involved the cleavage of peptides bound to major histocompatibility complex class II molecules of antigen presenting cells. May have a role in angiogenesis (By similarity). It is able to degrade Leu-enkephalin and Met-enkephalin but not cholecystokinin CCK8, neuromedin C (GRP-10), somatostatin-14, substance P and vasoactive intestinal peptide. In case of porcine transmissible gastroenteritis coronavirus (TGEV) and porcine respiratory coronavirus (PRCoV) infections, serves as a receptor for TGEV and PRCoV spike glycoprotein in a species-specific manner.<ref>PMID:7913510</ref> <ref>PMID:1350661</ref> <ref>PMID:7911642</ref> <ref>PMID:8985407</ref> <ref>PMID:9634079</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The M1 family of metalloproteases represents a large number of exopeptidases that cleave single amino acid residues from the N-terminus of peptide substrates. One member of this family that has been well studied is aminopeptidase N (APN), a multifunctional protease known to cleave biologically active peptides and aide in coronavirus entry. The proteolytic activity of APN promotes cancer angiogenesis and metastasis making it an important target for cancer therapy. To understand the substrate specificity of APN for the development of targeted inhibitors, we used a global substrate profiling method to determine the P1-P4' amino acid preferences. The key structural features of the APN pharmacophore required for substrate recognition were elucidated by x-ray crystallography. By combining these substrate profiling and structural data, we were able to design a selective peptide inhibitor of APN that was an effective therapeutic both in vitro and in vivo against APN-expressing prostate cancer models.
-Authors: Chen, L., Lin, Y.-L., Li, F.
+The Rational Design of Therapeutic Peptides for Aminopeptidase N using a Substrate-Based Approach.,Joshi S, Chen L, Winter MB, Lin YL, Yang Y, Shapovalova M, Smith PM, Liu C, Li F, LeBeau AM Sci Rep. 2017 May 2;7(1):1424. doi: 10.1038/s41598-017-01542-5. PMID:28465619<ref>PMID:28465619</ref>
-Description: Crystal structure of porcine aminopeptidase-N with Methionine
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Lin, Y.-L]]
+<div class="pdbe-citations 6bv4" style="background-color:#fffaf0;"></div>
-[[Category: Li, F]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Membrane alanyl aminopeptidase]]
 [[Category: Chen, L]]
+[[Category: Li, F]]
+[[Category: Lin, Y L]]
+[[Category: Hydrolase]]
+[[Category: Zinc aminopeptidase]]

6bv4

From Proteopedia

Revision as of 08:32, 10 January 2018

Crystal structure of porcine aminopeptidase-N with Methionine

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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