4er4: Difference between revisions
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< | ==HIGH-RESOLUTION X-RAY ANALYSES OF RENIN INHIBITOR-ASPARTIC PROTEINASE COMPLEXES== | ||
<StructureSection load='4er4' size='340' side='right'caption='[[4er4]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4er4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ER4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ER4 FirstGlance]. <br> | |||
or | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LAV:N-[(2S)-2-AMINO-4-METHYLPENTYL]-L-VALINE'>LAV</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=4er4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4er4 OCA], [https://pdbe.org/4er4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4er4 RCSB], [https://www.ebi.ac.uk/pdbsum/4er4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4er4 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CARP_CRYPA CARP_CRYPA] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/er/4er4_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=4er4 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Inhibitors of the conversion of angiotensinogen to the vasoconstrictor angiotensin II have considerable value as antihypertensive agents. For example, captopril and enalapril are clinically useful as inhibitors of angiotensin-converting enzyme. This has encouraged intense activity in the development of inhibitors of kidney renin, which is a very specific aspartic proteinase catalysing the first and rate limiting step in the conversion of angiotensinogen to angiotensin II. The most effective inhibitors such as H-142 and L-363,564 have used non-hydrolysable analogues of the proposed transition state, and partial sequences of angiotensinogen (Table 1). H-142 is effective in lowering blood pressure in humans but has no significant effect on other aspartic proteinases such as pepsin in the human body (Table 1). At present there are no crystal structures available for human or mouse renins although three-dimensional models demonstrate close structural similarity to other spartic proteinases. We have therefore determined by X-ray analysis the three-dimensional structures of H-142 and L-363,564 complexed with the aspartic proteinase endothiapepsin, which binds these inhibitors with affinities not greatly different from those measured against human renin (Table 1). The structures of these complexes and of that between endothiapepsin and the general aspartic proteinase inhibitor, H-256 (Table 1) define the common hydrogen bonding schemes that allow subtle differences in side-chain orientations and in the positions of the transition state analogues with respect to the active-site aspartates. | |||
High resolution X-ray analyses of renin inhibitor-aspartic proteinase complexes.,Foundling SI, Cooper J, Watson FE, Cleasby A, Pearl LH, Sibanda BL, Hemmings A, Wood SP, Blundell TL, Valler MJ, et al. Nature. 1987 May 28-Jun 3;327(6120):349-52. PMID:3295561<ref>PMID:3295561</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4er4" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Pepsin|Pepsin]] | |||
*[[Proteinase 3D structures|Proteinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
== | </StructureSection> | ||
== | |||
< | |||
[[Category: Cryphonectria parasitica]] | [[Category: Cryphonectria parasitica]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Blundell | [[Category: Blundell TL]] | ||
[[Category: Foundling | [[Category: Foundling SI]] | ||
[[Category: Szelke | [[Category: Szelke M]] | ||
[[Category: Watson | [[Category: Watson FE]] | ||
Latest revision as of 12:58, 30 October 2024
HIGH-RESOLUTION X-RAY ANALYSES OF RENIN INHIBITOR-ASPARTIC PROTEINASE COMPLEXESHIGH-RESOLUTION X-RAY ANALYSES OF RENIN INHIBITOR-ASPARTIC PROTEINASE COMPLEXES
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedInhibitors of the conversion of angiotensinogen to the vasoconstrictor angiotensin II have considerable value as antihypertensive agents. For example, captopril and enalapril are clinically useful as inhibitors of angiotensin-converting enzyme. This has encouraged intense activity in the development of inhibitors of kidney renin, which is a very specific aspartic proteinase catalysing the first and rate limiting step in the conversion of angiotensinogen to angiotensin II. The most effective inhibitors such as H-142 and L-363,564 have used non-hydrolysable analogues of the proposed transition state, and partial sequences of angiotensinogen (Table 1). H-142 is effective in lowering blood pressure in humans but has no significant effect on other aspartic proteinases such as pepsin in the human body (Table 1). At present there are no crystal structures available for human or mouse renins although three-dimensional models demonstrate close structural similarity to other spartic proteinases. We have therefore determined by X-ray analysis the three-dimensional structures of H-142 and L-363,564 complexed with the aspartic proteinase endothiapepsin, which binds these inhibitors with affinities not greatly different from those measured against human renin (Table 1). The structures of these complexes and of that between endothiapepsin and the general aspartic proteinase inhibitor, H-256 (Table 1) define the common hydrogen bonding schemes that allow subtle differences in side-chain orientations and in the positions of the transition state analogues with respect to the active-site aspartates. High resolution X-ray analyses of renin inhibitor-aspartic proteinase complexes.,Foundling SI, Cooper J, Watson FE, Cleasby A, Pearl LH, Sibanda BL, Hemmings A, Wood SP, Blundell TL, Valler MJ, et al. Nature. 1987 May 28-Jun 3;327(6120):349-52. PMID:3295561[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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