View source for 5inw


==Structure of reaction loop cleaved lamprey angiotensinogen==
<StructureSection load='5inw' size='340' side='right'caption='[[5inw]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5inw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lampetra_fluviatilis Lampetra fluviatilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5INW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5INW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5inw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5inw OCA], [https://pdbe.org/5inw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5inw RCSB], [https://www.ebi.ac.uk/pdbsum/5inw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5inw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C0MNC6_LAMFL C0MNC6_LAMFL] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lamprey angiotensinogen (l-ANT) is a hormone carrier in the regulation of blood pressure, but it is also a heparin-dependent thrombin inhibitor in lamprey blood coagulation system. The detailed mechanisms on how angiotensin is carried by l-ANT and how heparin binds l-ANT and mediates thrombin inhibition are unclear. Here we have solved the crystal structure of cleaved l-ANT at 2.7 angstrom resolution and characterized its properties in heparin binding and protease inhibition. The structure reveals that l-ANT has a conserved serpin fold with a labile N-terminal angiotensin peptide and undergoes a typical stressed-to-relaxed conformational change when the reactive center loop is cleaved. Heparin binds l-ANT tightly with a dissociation constant of ~10 nM involving ~8 monosaccharides and ~6 ionic interactions. The heparin binding site is located in an extensive positively charged surface area around helix D involving residues Lys148, Lys 151, Arg155 and Arg380. Although l-ANT by itself is a poor thrombin inhibitor with a second order rate constant of 500 M-1s-1, its interaction with thrombin is accelerated 90-fold by high-molecular-weight heparin following a bell-shaped dose dependent curve. Short heparin chains of 6-20 monosaccharide units are insufficient to promote thrombin inhibition. Furthermore, an l-ANT mutant with the P1 Ile mutated to Arg inhibits thrombin nearly 1500-fold faster than the wild type which is further accelerated by high-molecular-weight heparin. Taken together, these results suggest that heparin binds l-ANT at a conserved heparin binding site around helix D and promotes the interaction between l-ANT and thrombin through a conserved template mechanism of vertebrates.

Heparin binds lamprey angiotensinogen and promotes thrombin inhibition through a template mechanism.,Wei H, Cai H, Wu J, Wei Z, Zhang F, Huang X, Ma L, Feng L, Zhang R, Wang Y, Ragg H, Zheng Y, Zhou A J Biol Chem. 2016 Sep 28. pii: jbc.M116.725895. PMID:27681598<ref>PMID:27681598</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5inw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Lampetra fluviatilis]]
[[Category: Large Structures]]
[[Category: Wei H]]
[[Category: Zhou A]]