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1oph

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Revision as of 07:39, 15 February 2018

NON-COVALENT COMPLEX BETWEEN ALPHA-1-PI-PITTSBURGH AND S195A TRYPSIN

Structural highlights

1oph is a 2 chain structure with sequence from Bovin and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1oo8, 1qlp, 1ejm
Gene:	SERPINA1 OR PI OR AAT (HUMAN)
Activity:	Trypsin, with EC number 3.4.21.4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[A1AT_HUMAN] Defects in SERPINA1 are the cause of alpha-1-antitrypsin deficiency (A1ATD) [MIM:613490]. A disorder whose most common manifestation is emphysema, which becomes evident by the third to fourth decade. A less common manifestation of the deficiency is liver disease, which occurs in children and adults, and may result in cirrhosis and liver failure. Environmental factors, particularly cigarette smoking, greatly increase the risk of emphysema at an earlier age.^[1] ^[2] ^[3]

Function

[A1AT_HUMAN] Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin.[:]^[4] ^[5] Short peptide from AAT: reversible chymotrypsin inhibitor. It also inhibits elastase, but not trypsin. Its major physiological function is the protection of the lower respiratory tract against proteolytic destruction by human leukocyte elastase (HLE).[:]^[6] ^[7]

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 serpin antithrombin is a slow thrombin inhibitor that requires heparin to enhance its reaction rate. In contrast, alpha1-proteinase inhibitor (alpha1PI) Pittsburgh (P1 Met --> Arg natural variant) inhibits thrombin 17 times faster than pentasaccharide heparin-activated antithrombin. We present here x-ray structures of free and S195A trypsin-bound alpha1PI Pittsburgh, which show that the reactive center loop (RCL) possesses a canonical conformation in the free serpin that does not change upon binding to S195A trypsin and that contacts the proteinase only between P2 and P2'. By inference from the structure of heparin cofactor II bound to S195A thrombin, this RCL conformation is also appropriate for binding to thrombin. Reaction rates of trypsin and thrombin with alpha1PI Pittsburgh and antithrombin and their P2 variants show that the low antithrombin-thrombin reaction rate results from the antithrombin RCL sequence at P2 and implies that, in solution, the antithrombin RCL must be in a similar canonical conformation to that found here for alpha1PI Pittsburgh, even in the nonheparin-activated state. This suggests a general, limited, canonical-like interaction between serpins and proteinases in their Michaelis complexes.

Canonical inhibitor-like interactions explain reactivity of alpha1-proteinase inhibitor Pittsburgh and antithrombin with proteinases.,Dementiev A, Simonovic M, Volz K, Gettins PG J Biol Chem. 2003 Sep 26;278(39):37881-7. Epub 2003 Jul 14. PMID:12860985^[8]

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

References

↑ Seyama K, Nukiwa T, Takabe K, Takahashi H, Miyake K, Kira S. Siiyama (serine 53 (TCC) to phenylalanine 53 (TTC)). A new alpha 1-antitrypsin-deficient variant with mutation on a predicted conserved residue of the serpin backbone. J Biol Chem. 1991 Jul 5;266(19):12627-32. PMID:1905728
↑ Holmes MD, Brantly ML, Fells GA, Crystal RG. Alpha 1-antitrypsin Wbethesda: molecular basis of an unusual alpha 1-antitrypsin deficiency variant. Biochem Biophys Res Commun. 1990 Aug 16;170(3):1013-20. PMID:2390072
↑ Graham A, Kalsheker NA, Bamforth FJ, Newton CR, Markham AF. Molecular characterisation of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null(Newport) (Gly115----Ser) and (Pi) Z Wrexham (Ser-19----Leu). Hum Genet. 1990 Oct;85(5):537-40. PMID:2227940
↑ Tanaka N, Sekiya S, Takamizawa H, Kato N, Moriyama Y, Fujimura S. Characterization of a 54 kDa, alpha 1-antitrypsin-like protein isolated from ascitic fluid of an endometrial cancer patient. Jpn J Cancer Res. 1991 Jun;82(6):693-700. PMID:1906855
↑ Niemann MA, Narkates AJ, Miller EJ. Isolation and serine protease inhibitory activity of the 44-residue, C-terminal fragment of alpha 1-antitrypsin from human placenta. Matrix. 1992 Jun;12(3):233-41. PMID:1406456
↑ Tanaka N, Sekiya S, Takamizawa H, Kato N, Moriyama Y, Fujimura S. Characterization of a 54 kDa, alpha 1-antitrypsin-like protein isolated from ascitic fluid of an endometrial cancer patient. Jpn J Cancer Res. 1991 Jun;82(6):693-700. PMID:1906855
↑ Niemann MA, Narkates AJ, Miller EJ. Isolation and serine protease inhibitory activity of the 44-residue, C-terminal fragment of alpha 1-antitrypsin from human placenta. Matrix. 1992 Jun;12(3):233-41. PMID:1406456
↑ Dementiev A, Simonovic M, Volz K, Gettins PG. Canonical inhibitor-like interactions explain reactivity of alpha1-proteinase inhibitor Pittsburgh and antithrombin with proteinases. J Biol Chem. 2003 Sep 26;278(39):37881-7. Epub 2003 Jul 14. PMID:12860985 doi:http://dx.doi.org/10.1074/jbc.M305195200

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1oph"

@@ Line 1: / Line 1: @@
 ==NON-COVALENT COMPLEX BETWEEN ALPHA-1-PI-PITTSBURGH AND S195A TRYPSIN==
 <StructureSection load='1oph' size='340' side='right' caption='[[1oph]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SERPINA1 OR PI OR AAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] </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=1oph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oph OCA], [http://pdbe.org/1oph PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1oph RCSB], [http://www.ebi.ac.uk/pdbsum/1oph PDBsum]</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=1oph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oph OCA], [http://pdbe.org/1oph PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1oph RCSB], [http://www.ebi.ac.uk/pdbsum/1oph PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1oph ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/op/1oph_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/op/1oph_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1oph ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 31: / Line 32: @@
 </div>
 <div class="pdbe-citations 1oph" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Alpha-1-antitrypsin|Alpha-1-antitrypsin]]
-*[[Trypsin|Trypsin]]
 == References ==
 <references/>

1oph

From Proteopedia

Revision as of 07:39, 15 February 2018

NON-COVALENT COMPLEX BETWEEN ALPHA-1-PI-PITTSBURGH AND S195A TRYPSIN

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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