User:Daniel Seeman/Alpha-1-antitrypsin: Difference between revisions
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{{STRUCTURE_1atu | PDB=1atu1ezxwd.pdb | SCENE=User:Daniel_Seeman/Alpha-1-antitrypsin/437437437437/1}} | {{STRUCTURE_1atu | PDB=1atu1ezxwd.pdb | SCENE=User:Daniel_Seeman/Alpha-1-antitrypsin/437437437437/1}} | ||
'''Alpha-1-antitrypsin''' ( | '''Alpha-1-antitrypsin''' (also known as α1-antitrypsin or A1AT) is an inhibitor of [[Elastase]] and [[Trypsin]]. It is a member of the '''Ser'''ine '''P'''rotease '''I'''nhibitor ([[:Category:Serpin|Serpin]]) family, and as such undergoes a conformational change where the substrate protein associates with a loop region on A1AT causing that loop to become ordered as a Beta Strand<ref name="nature_paper">''Nature'' '''455''', 1189-1190 (30 October 2008)</ref>. In this case Trypsin (the substrate) is inhibited when a covalent bond is formed to A1AT through the newly formed Beta region<ref name="nature_paper" />. Once bound covalently to its substrate the stability of the A1AT complex goes up drastically<ref name="nature_paper" />. With A1AT, as with most members of the Serpin family, the transition from inactive precursor protein to active complex comes after a cleavage event<ref name="nature_paper" />. Shown <scene name='User:Daniel_Seeman/Alpha-1-antitrypsin/437437437437/1'>on the right</scene> is a morph, generated by the <span class="plainlinks">[http://molmovdb.mbb.yale.edu/molmovdb/morph/ Yale Morph Server]</span> that shows A1AT going from its inactive form, to the conformation in which it is bound to Trypsin (also shown in the same animation)<ref>The <span class="plainlinks">[http://molmovdb.mbb.yale.edu/molmovdb/morph/ Yale Morph Server]</span></ref>. | ||
=== Role in disease === | === Role in disease === | ||
Revision as of 16:23, 2 December 2008
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| 1atu, resolution 2.70Å () | |||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Alpha-1-antitrypsin (also known as α1-antitrypsin or A1AT) is an inhibitor of Elastase and Trypsin. It is a member of the Serine Protease Inhibitor (Serpin) family, and as such undergoes a conformational change where the substrate protein associates with a loop region on A1AT causing that loop to become ordered as a Beta Strand[1]. In this case Trypsin (the substrate) is inhibited when a covalent bond is formed to A1AT through the newly formed Beta region[1]. Once bound covalently to its substrate the stability of the A1AT complex goes up drastically[1]. With A1AT, as with most members of the Serpin family, the transition from inactive precursor protein to active complex comes after a cleavage event[1]. Shown is a morph, generated by the Yale Morph Server that shows A1AT going from its inactive form, to the conformation in which it is bound to Trypsin (also shown in the same animation)[2].
Role in diseaseRole in disease
Mutations of MET358 to ARG can lead to a change in specificity in the Elastase binding pocket, essentially turning the M358R mutant of A1AT into a Thrombin inhibitor by generating specificity for this new substrate. This drop in Thrombin levels can lead to hemorrhaging. [3]