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9api

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Revision as of 11:46, 5 August 2016

THE S VARIANT OF HUMAN ALPHA1-ANTITRYPSIN, STRUCTURE AND IMPLICATIONS FOR FUNCTION AND METABOLISM

Structural highlights

9api is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	7api, 8api
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 S variant of the human alpha 1-antitrypsin with E-264----V, is responsible for a mild alpha 1-antitrypsin deficiency quite common in the European population. S protein specifically cleaved at the susceptible peptide bond was crystallized and its crystal structure determined and refined to 3.1 A resolution. The S variant crystallizes isomorphous to the normal M variant. The difference Fourier electron density map shows the E----V change as outstanding residual density. In addition, small structural changes of the main polypeptide chain radiate from the site of mutation and affect parts far removed from it. By the mutation, internal hydrogen bonds and salt linkages of E-264 to Y-38 and K-487, respectively, are lost. They cause the far-reaching slight distortions and are probably related to the reduced thermal stability of the S mutant. They may also be responsible for slower folding of the polypeptide chain and the clinical symptoms of alpha 1-antitrypsin deficiency. In a theoretical study by molecular dynamics methods simulations of the M and S proteins were made and the results analysed with respect to structural and dynamic properties and compared with the experimental results. There is a significant correlation between experimental and theoretical results in some respects.

The S variant of human alpha 1-antitrypsin, structure and implications for function and metabolism.,Engh R, Lobermann H, Schneider M, Wiegand G, Huber R, Laurell CB Protein Eng. 1989 Mar;2(6):407-15. PMID:2785270^[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
↑ Engh R, Lobermann H, Schneider M, Wiegand G, Huber R, Laurell CB. The S variant of human alpha 1-antitrypsin, structure and implications for function and metabolism. Protein Eng. 1989 Mar;2(6):407-15. PMID:2785270

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9api"

Categories: Deisenhofer, J | Huber, R | Loebermann, H | Tokuoka, R | Proteinase inhibitor

@@ Line 1: / Line 1: @@
 ==THE S VARIANT OF HUMAN ALPHA1-ANTITRYPSIN, STRUCTURE AND IMPLICATIONS FOR FUNCTION AND METABOLISM==
 <StructureSection load='9api' size='340' side='right' caption='[[9api]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[7api|7api]], [[8api|8api]]</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=9api FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9api OCA], [http://www.rcsb.org/pdb/explore.do?structureId=9api RCSB], [http://www.ebi.ac.uk/pdbsum/9api 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=9api FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9api OCA], [http://pdbe.org/9api PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=9api RCSB], [http://www.ebi.ac.uk/pdbsum/9api PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=9api ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
     <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=9api ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 29: / Line 30: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 9api" style="background-color:#fffaf0;"></div>
 ==See Also==

9api

From Proteopedia

Revision as of 11:46, 5 August 2016

THE S VARIANT OF HUMAN ALPHA1-ANTITRYPSIN, STRUCTURE AND IMPLICATIONS FOR FUNCTION AND METABOLISM

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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