|
|
| Line 3: |
Line 3: |
| | <StructureSection load='3mc2' size='340' side='right'caption='[[3mc2]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='3mc2' size='340' side='right'caption='[[3mc2]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3mc2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MC2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MC2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3mc2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MC2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MC2 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">1300017J02Rik, mICA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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]] 2.4Å</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=3mc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mc2 OCA], [https://pdbe.org/3mc2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mc2 RCSB], [https://www.ebi.ac.uk/pdbsum/3mc2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mc2 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=3mc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mc2 OCA], [https://pdbe.org/3mc2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mc2 RCSB], [https://www.ebi.ac.uk/pdbsum/3mc2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mc2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ICA_MOUSE ICA_MOUSE]] Inhibitor for carbonic anhydrase 2 (CA2). Does not bind iron ions.<ref>PMID:17511619</ref> <ref>PMID:18712936</ref>
| + | [https://www.uniprot.org/uniprot/ICA_MOUSE ICA_MOUSE] Inhibitor for carbonic anhydrase 2 (CA2). Does not bind iron ions.<ref>PMID:17511619</ref> <ref>PMID:18712936</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 14: |
Line 14: |
| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mc/3mc2_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mc/3mc2_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> |
| Line 33: |
Line 33: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Eckenroth, B E]] | + | [[Category: Eckenroth BE]] |
| - | [[Category: Everse, S J]] | + | [[Category: Everse SJ]] |
| - | [[Category: Mason, A B]] | + | [[Category: Mason AB]] |
| - | [[Category: Lyase inhibitor]]
| + | |
| - | [[Category: Mica]]
| + | |
| - | [[Category: Transferrin superfamily]]
| + | |
| Structural highlights
Function
ICA_MOUSE Inhibitor for carbonic anhydrase 2 (CA2). Does not bind iron ions.[1] [2]
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 original signature of the transferrin (TF) family of proteins was the ability to bind ferric iron with high affinity in the cleft of each of two homologous lobes. However, in recent years new family members which do not bind iron have been discovered. One new member is the inhibitor of carbonic anhydrase (ICA), which as its name indicates, binds to and strongly inhibits certain isoforms of carbonic anhydrase. Recently mouse ICA has been expressed as a recombinant protein in a mammalian cell system. Here we describe the 2.4 A structure of mouse ICA from a pseudomerohedral twinned crystal. As predicted, the structure is bilobal, comprised of two alpha-beta domains per lobe typical of the other family members; as with all but insect TFs, the structure includes the unusual reverse gamma-turn in each lobe. The structure is consistent with the fact that introduction of two mutations in the N-lobe of mICA (W124R and S188Y) allowed it to bind iron with high affinity. Unexpectedly, both lobes of the mICA were found in the closed conformation usually associated with presence of iron in the cleft, and making the structure most similar to diferric pig TF. Two new ICA family members (guinea pig and horse) were identified from genomic sequences and used in evolutionary comparisons. Additionally, a comparison of selection pressure (dN/dS) on functional residues reveals some interesting insights into the evolution of the TF family including that the N-lobe of lactoferrin may be in the process of eliminating its iron binding function.
The structure and evolution of the murine inhibitor of carbonic anhydrase: A member of the transferrin superfamily.,Eckenroth BE, Mason AB, McDevitt ME, Lambert LA, Everse SJ Protein Sci. 2010 Jun 23. PMID:20572014[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang F, Lothrop AP, James NG, Griffiths TA, Lambert LA, Leverence R, Kaltashov IA, Andrews NC, MacGillivray RT, Mason AB. A novel murine protein with no effect on iron homoeostasis is homologous with transferrin and is the putative inhibitor of carbonic anhydrase. Biochem J. 2007 Aug 15;406(1):85-95. PMID:17511619 doi:10.1042/BJ20070384
- ↑ Mason AB, Judson GL, Bravo MC, Edelstein A, Byrne SL, James NG, Roush ED, Fierke CA, Bobst CE, Kaltashov IA, Daughtery MA. Evolution reversed: the ability to bind iron restored to the N-lobe of the murine inhibitor of carbonic anhydrase by strategic mutagenesis. Biochemistry. 2008 Sep 16;47(37):9847-55. doi: 10.1021/bi801133d. Epub 2008 Aug, 20. PMID:18712936 doi:10.1021/bi801133d
- ↑ Eckenroth BE, Mason AB, McDevitt ME, Lambert LA, Everse SJ. The structure and evolution of the murine inhibitor of carbonic anhydrase: A member of the transferrin superfamily. Protein Sci. 2010 Jun 23. PMID:20572014 doi:10.1002/pro.439
|
