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2wcb

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Revision as of 08:32, 1 July 2020

S100A12 complex with zinc in the absence of calcium

Structural highlights

2wcb is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1gqm, 2wc8, 2wcf, 1odb, 1e8a, 2wce
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[S10AC_HUMAN] S100A12 is a calcium-, zinc- and copper-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. Its proinflammatory activity involves recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to receptor for advanced glycation endproducts (AGER). Binding to AGER activates the MAP-kinase and NF-kappa-B signaling pathways leading to production of proinflammatory cytokines and up-regulation of cell adhesion molecules ICAM1 and VCAM1. Acts as a monocyte and mast cell chemoattractant. Can stimulate mast cell degranulation and activation which generates chemokines, histamine and cytokines inducing further leukocyte recruitment to the sites of inflammation. Can inhibit the activity of matrix metalloproteinases; MMP2, MMP3 and MMP9 by chelating Zn(2+) from their active sites. Possesses filariacidal and filariastatic activity. Calcitermin possesses antifungal activity against C.albicans and is also active against E.coli and P.aeruginosa but not L.monocytogenes and S.aureus.^[1] ^[2] ^[3] ^[4]

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

The functions of the members of the S100 family of EF-hand proteins are modulated by calcium and, in a number of cases, by zinc or copper. One such protein is S100A12, which is implicated in inflammation and host-parasite responses. Previously, we reported the structures of human S100A12 in both low (dimeric) and high (hexameric) calcium forms and, in addition, that of a complex with copper and calcium. Here we report the crystal structures of the metal-free apo form of human S100A12 at 1.77 A resolution and of the zinc complex in two crystal forms (P2(1)2(1)2(1) and F222) to 1.88 A and 1.73 A resolution, respectively. These are the first structures of a zinc-only complex of an S100 protein to be determined. The zinc complex structure shows significant differences from those of both calcium-loaded and apo-S100A12 structures, and comparisons suggest an explanation for the zinc-induced 1500-fold increase in calcium affinity. In addition, the new structures provide insight into the role of zinc-calcium interplay in the transition of S100A12 from a dimer through a tetramer to a hexamer. The role of both zinc and calcium in target binding by S100A12 during host-parasite responses is confirmed by experiments with paramyosin from the tropical parasites Onchocerca volvulus and Brugia malayi.

The crystal structures of human S100A12 in apo form and in complex with zinc: new insights into S100A12 oligomerisation.,Moroz OV, Blagova EV, Wilkinson AJ, Wilson KS, Bronstein IB J Mol Biol. 2009 Aug 21;391(3):536-51. Epub 2009 Jun 6. PMID:19501594^[5]

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

References

↑ Cole AM, Kim YH, Tahk S, Hong T, Weis P, Waring AJ, Ganz T. Calcitermin, a novel antimicrobial peptide isolated from human airway secretions. FEBS Lett. 2001 Aug 24;504(1-2):5-10. PMID:11522286
↑ Yang Z, Yan WX, Cai H, Tedla N, Armishaw C, Di Girolamo N, Wang HW, Hampartzoumian T, Simpson JL, Gibson PG, Hunt J, Hart P, Hughes JM, Perry MA, Alewood PF, Geczy CL. S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity. J Allergy Clin Immunol. 2007 Jan;119(1):106-14. Epub 2006 Oct 6. PMID:17208591 doi:http://dx.doi.org/10.1016/j.jaci.2006.08.021
↑ Yan WX, Armishaw C, Goyette J, Yang Z, Cai H, Alewood P, Geczy CL. Mast cell and monocyte recruitment by S100A12 and its hinge domain. J Biol Chem. 2008 May 9;283(19):13035-43. doi: 10.1074/jbc.M710388200. Epub 2008 , Feb 21. PMID:18292089 doi:http://dx.doi.org/10.1074/jbc.M710388200
↑ Moroz OV, Burkitt W, Wittkowski H, He W, Ianoul A, Novitskaya V, Xie J, Polyakova O, Lednev IK, Shekhtman A, Derrick PJ, Bjoerk P, Foell D, Bronstein IB. Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function. BMC Biochem. 2009 Apr 23;10:11. doi: 10.1186/1471-2091-10-11. PMID:19386136 doi:http://dx.doi.org/10.1186/1471-2091-10-11
↑ Moroz OV, Blagova EV, Wilkinson AJ, Wilson KS, Bronstein IB. The crystal structures of human S100A12 in apo form and in complex with zinc: new insights into S100A12 oligomerisation. J Mol Biol. 2009 Aug 21;391(3):536-51. Epub 2009 Jun 6. PMID:19501594 doi:10.1016/j.jmb.2009.06.004

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2wcb"

@@ Line 1: / Line 1: @@
 ==S100A12 complex with zinc in the absence of calcium==
-<StructureSection load='2wcb' size='340' side='right' caption='[[2wcb]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
+<StructureSection load='2wcb' size='340' side='right'caption='[[2wcb]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2wcb]] is a 2 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=2WCB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WCB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2wcb]] is a 2 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=2WCB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2WCB FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gqm|1gqm]], [[2wc8|2wc8]], [[2wcf|2wcf]], [[1odb|1odb]], [[1e8a|1e8a]], [[2wce|2wce]]</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=2wcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wcb OCA], [http://pdbe.org/2wcb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wcb RCSB], [http://www.ebi.ac.uk/pdbsum/2wcb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wcb ProSAT]</span></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=2wcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wcb OCA], [http://pdbe.org/2wcb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wcb RCSB], [http://www.ebi.ac.uk/pdbsum/2wcb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wcb ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 31: / Line 31: @@
 ==See Also==
-*[[S100 protein|S100 protein]]
+*[[S100 proteins 3D structures|S100 proteins 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 37: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Blagova, E V]]
 [[Category: Bronstein, I B]]

2wcb

From Proteopedia

Revision as of 08:32, 1 July 2020

S100A12 complex with zinc in the absence of calcium

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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