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}}

'''Alpha-1-antitrypsin''' (or α1-antitrypsin, 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 a loop region becomes ordered as a Beta Strand<ref ~~name="biochem_text"~~>~~''Biochemistry'', Fifth Edition, p.289.~~</ref>. In this case Trypsin is inhibited when a covalent bond is formed to A1AT. With A1AT, as with most members of the Serpin family, the transition from inactive precursor protein to active complex comes after a cleavage event. Shown <scene name='User:Daniel_Seeman/Alpha-1-antitrypsin/437437437437/1'>on the right</scene> is a morph, generated by the [http://molmovdb.mbb.yale.edu/molmovdb/morph/ 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)<ref>The [http://molmovdb.mbb.yale.edu/molmovdb/morph/ Yale Morph Server]</ref>.

'''Alpha-1-antitrypsin''' (or α1-antitrypsin, 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 a loop region becomes ordered as a Beta Strand<ref>reference</ref>. In this case Trypsin is inhibited when a covalent bond is formed to A1AT. With A1AT, as with most members of the Serpin family, the transition from inactive precursor protein to active complex comes after a cleavage event. Shown <scene name='User:Daniel_Seeman/Alpha-1-antitrypsin/437437437437/1'>on the right</scene> is a morph, generated by the [http://molmovdb.mbb.yale.edu/molmovdb/morph/ 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)<ref>The [http://molmovdb.mbb.yale.edu/molmovdb/morph/ Yale Morph Server]</ref>.

=== Role 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. <ref ~~name="biochem_text"~~ />

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. <ref>''Biochemistry'', Fifth Edition, p.289.</ref>

=== Scenes ===

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 {{STRUCTURE_1atu |  PDB=1atu1ezxwd.pdb  |   SCENE=User:Daniel_Seeman/Alpha-1-antitrypsin/437437437437/1}}
-'''Alpha-1-antitrypsin''' (or α1-antitrypsin, 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 a loop region becomes ordered as a Beta Strand<ref name="biochem_text">''Biochemistry'', Fifth Edition, p.289.</ref>.  In this case Trypsin is inhibited when a covalent bond is formed to A1AT.  With A1AT, as with most members of the Serpin family, the transition from inactive precursor protein to active complex comes after a cleavage event.  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>.
+'''Alpha-1-antitrypsin''' (or α1-antitrypsin, 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 a loop region becomes ordered as a Beta Strand<ref>reference</ref>.  In this case Trypsin is inhibited when a covalent bond is formed to A1AT.  With A1AT, as with most members of the Serpin family, the transition from inactive precursor protein to active complex comes after a cleavage event.  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 ===
-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.  <ref name="biochem_text" />
+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.  <ref>''Biochemistry'', Fifth Edition, p.289.</ref>
 === Scenes ===