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| | <StructureSection load='2nsm' size='340' side='right'caption='[[2nsm]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='2nsm' size='340' side='right'caption='[[2nsm]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2nsm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NSM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2NSM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2nsm]] 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=2NSM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NSM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysine_carboxypeptidase Lysine carboxypeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.3 3.4.17.3] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2nsm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nsm OCA], [http://pdbe.org/2nsm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2nsm RCSB], [http://www.ebi.ac.uk/pdbsum/2nsm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2nsm ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2nsm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nsm OCA], [https://pdbe.org/2nsm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nsm RCSB], [https://www.ebi.ac.uk/pdbsum/2nsm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nsm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CBPN_HUMAN CBPN_HUMAN]] Defects in CPN1 are the cause of carboxypeptidase N deficiency (CPND) [MIM:[http://omim.org/entry/212070 212070]]. Patients affected present some combination of angioedema or chronic urticaria, as well as hay fever or astma, and have also slightly depressed serum carboxy peptidase N, suggestive of autosomal recessive inheritance of this disorder.<ref>PMID:12560874</ref> | + | [https://www.uniprot.org/uniprot/CBPN_HUMAN CBPN_HUMAN] Defects in CPN1 are the cause of carboxypeptidase N deficiency (CPND) [MIM:[https://omim.org/entry/212070 212070]. Patients affected present some combination of angioedema or chronic urticaria, as well as hay fever or astma, and have also slightly depressed serum carboxy peptidase N, suggestive of autosomal recessive inheritance of this disorder.<ref>PMID:12560874</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CBPN_HUMAN CBPN_HUMAN]] Protects the body from potent vasoactive and inflammatory peptides containing C-terminal Arg or Lys (such as kinins or anaphylatoxins) which are released into the circulation. | + | [https://www.uniprot.org/uniprot/CBPN_HUMAN CBPN_HUMAN] Protects the body from potent vasoactive and inflammatory peptides containing C-terminal Arg or Lys (such as kinins or anaphylatoxins) which are released into the circulation. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ns/2nsm_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ns/2nsm_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lysine carboxypeptidase]]
| + | [[Category: Bode W]] |
| - | [[Category: Bode, W]] | + | [[Category: Deddish PA]] |
| - | [[Category: Deddish, P A]] | + | [[Category: Erdoes EG]] |
| - | [[Category: Erdoes, E G]] | + | [[Category: Hoopes JT]] |
| - | [[Category: Hoopes, J T]] | + | [[Category: Huber R]] |
| - | [[Category: Huber, R]] | + | [[Category: Keil C]] |
| - | [[Category: Keil, C]] | + | [[Category: Maskos K]] |
| - | [[Category: Maskos, K]] | + | [[Category: Skidgel RA]] |
| - | [[Category: Skidgel, R A]] | + | [[Category: Tan F]] |
| - | [[Category: Tan, F]] | + | [[Category: Than M]] |
| - | [[Category: Than, M]] | + | |
| - | [[Category: Caroxypeptidase]]
| + | |
| - | [[Category: Hormone processing]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Peptide modification]]
| + | |
| - | [[Category: Transthyretin-like domain]]
| + | |
| - | [[Category: Zinc peptidase]]
| + | |
| Structural highlights
Disease
CBPN_HUMAN Defects in CPN1 are the cause of carboxypeptidase N deficiency (CPND) [MIM:212070. Patients affected present some combination of angioedema or chronic urticaria, as well as hay fever or astma, and have also slightly depressed serum carboxy peptidase N, suggestive of autosomal recessive inheritance of this disorder.[1]
Function
CBPN_HUMAN Protects the body from potent vasoactive and inflammatory peptides containing C-terminal Arg or Lys (such as kinins or anaphylatoxins) which are released into the circulation.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human carboxypeptidase N (CPN), a member of the CPN/E subfamily of "regulatory" metallo-carboxypeptidases, is an extracellular glycoprotein synthesized in the liver and secreted into the blood, where it controls the activity of vasoactive peptide hormones, growth factors and cytokines by specifically removing C-terminal basic residues. Normally, CPN circulates in blood plasma as a hetero-tetramer consisting of two 83 kDa (CPN2) domains each flanked by a 48 to 55 kDa catalytic (CPN1) domain. We have prepared and crystallized the recombinant C-terminally truncated catalytic domain of human CPN1, and have determined and refined its 2.1 A crystal structure. The structural analysis reveals that CPN1 has a pear-like shape, consisting of a 319 residue N-terminal catalytic domain and an abutting, cylindrically shaped 79 residue C-terminal beta-sandwich transthyretin (TT) domain, more resembling CPD-2 than CPM. Like these other CPN/E members, two surface loops surrounding the active-site groove restrict access to the catalytic center, offering an explanation for why some larger protein carboxypeptidase inhibitors do not inhibit CPN. Modeling of the Pro-Phe-Arg C-terminal end of the natural substrate bradykinin into the active site shows that the S1' pocket of CPN1 might better accommodate P1'-Lys than Arg residues, in agreement with CPN's preference for cleaving off C-terminal Lys residues. Three Thr residues at the distal TT edge of CPN1 are O-linked to N-acetyl glucosamine sugars; equivalent sites in the membrane-anchored CPM are occupied by basic residues probably involved in membrane interaction. In tetrameric CPN, each CPN1 subunit might interact with the central leucine-rich repeat tandem of the cognate CPN2 subunit via a unique hydrophobic surface patch wrapping around the catalytic domain-TT interface, exposing the two active centers.
Crystal structure of the human carboxypeptidase N (kininase I) catalytic domain.,Keil C, Maskos K, Than M, Hoopes JT, Huber R, Tan F, Deddish PA, Erdos EG, Skidgel RA, Bode W J Mol Biol. 2007 Feb 16;366(2):504-16. Epub 2006 Nov 11. PMID:17157876[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cao H, Hegele RA. DNA polymorphism and mutations in CPN1, including the genomic basis of carboxypeptidase N deficiency. J Hum Genet. 2003;48(1):20-2. PMID:12560874 doi:10.1007/s100380300003
- ↑ Keil C, Maskos K, Than M, Hoopes JT, Huber R, Tan F, Deddish PA, Erdos EG, Skidgel RA, Bode W. Crystal structure of the human carboxypeptidase N (kininase I) catalytic domain. J Mol Biol. 2007 Feb 16;366(2):504-16. Epub 2006 Nov 11. PMID:17157876 doi:10.1016/j.jmb.2006.11.025
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