|
|
| Line 1: |
Line 1: |
| | | | |
| | ==CLEAVED ANTICHYMOTRYPSIN A347R== | | ==CLEAVED ANTICHYMOTRYPSIN A347R== |
| - | <StructureSection load='3caa' size='340' side='right' caption='[[3caa]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='3caa' size='340' side='right'caption='[[3caa]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3caa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2caa 2caa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CAA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CAA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3caa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2caa 2caa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CAA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CAA FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3caa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3caa OCA], [http://pdbe.org/3caa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3caa RCSB], [http://www.ebi.ac.uk/pdbsum/3caa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3caa 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=3caa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3caa OCA], [https://pdbe.org/3caa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3caa RCSB], [https://www.ebi.ac.uk/pdbsum/3caa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3caa ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AACT_HUMAN AACT_HUMAN]] Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2.<ref>PMID:2404007</ref> | + | [[https://www.uniprot.org/uniprot/AACT_HUMAN AACT_HUMAN]] Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2.<ref>PMID:2404007</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 30: |
Line 30: |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Serpin|Serpin]] | + | *[[Serpin 3D structures|Serpin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 36: |
Line 36: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Christianson, D W]] | | [[Category: Christianson, D W]] |
| | [[Category: Lukacs, C M]] | | [[Category: Lukacs, C M]] |
| Structural highlights
Function
[AACT_HUMAN] Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2.[1]
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
Expressed in a kinetically trapped folding state, a serpin couples the thermodynamic driving force of a massive beta-sheet rearrangement to the inhibition of a target protease. Hence, the serpin-protease interaction is the premier example of a "spring-loaded" protein-protein interaction. Amino acid substitutions in the hinge region of a serpin reactive loop can weaken the molecular spring, which converts the serpin from an inhibitor into a substrate. To probe the molecular basis of this conversion, we report the crystal structure of A349R antichymotrypsin in the reactive loop cleaved state at 2.1 A resolution. This amino acid substitution does not block the beta-sheet rearrangement despite the burial of R349 in the hydrophobic core of the cleaved serpin along with a salt-linked acetate ion. The inhibitory activity of this serpin variant is not obliterated; remarkably, its inhibitory properties are anion-dependent due to the creation of an anion-binding cavity in the cleaved serpin.
Engineering an anion-binding cavity in antichymotrypsin modulates the "spring-loaded" serpin-protease interaction.,Lukacs CM, Rubin H, Christianson DW Biochemistry. 1998 Mar 10;37(10):3297-304. PMID:9521649[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rubin H, Wang ZM, Nickbarg EB, McLarney S, Naidoo N, Schoenberger OL, Johnson JL, Cooperman BS. Cloning, expression, purification, and biological activity of recombinant native and variant human alpha 1-antichymotrypsins. J Biol Chem. 1990 Jan 15;265(2):1199-207. PMID:2404007
- ↑ Lukacs CM, Rubin H, Christianson DW. Engineering an anion-binding cavity in antichymotrypsin modulates the "spring-loaded" serpin-protease interaction. Biochemistry. 1998 Mar 10;37(10):3297-304. PMID:9521649 doi:10.1021/bi972359e
|
