1bil: Difference between revisions

Latest revision as of 04:24, 17 October 2024

CRYSTALLOGRAPHIC STUDIES ON THE BINDING MODES OF P2-P3 BUTANEDIAMIDE RENIN INHIBITORS

Structural highlights

1bil is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	0IU
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

RENI_HUMAN Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:267430. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).^[1] Defects in REN are the cause of familial juvenile hyperuricemic nephropathy type 2 (HNFJ2) [MIM:613092. It is a renal disease characterized by juvenile onset of hyperuricemia, slowly progressive renal failure and anemia.^[2]

Function

RENI_HUMAN Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.

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 binding modes of three peptidomimetic P2-P3 butanediamide renin inhibitors have been determined by x-ray crystallography. The inhibitors are bound with their backbones in an extended conformation, and their side chains occupying the S5 to S1' pockets. A (2-amino-4-thiazolyl)methyl side chain at the P2 position shows stronger hydrogen-bonding and van der Waals interactions with renin than the His side chain, which is present in the natural substrate. The ACHPA-gamma-lactam transition state analog has similar interactions with renin as the dihydroxyethylene transition state analog.

Crystallographic studies on the binding modes of P2-P3 butanediamide renin inhibitors.,Tong L, Pav S, Lamarre D, Simoneau B, Lavallee P, Jung G J Biol Chem. 1995 Dec 8;270(49):29520-4. PMID:7493993^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gribouval O, Gonzales M, Neuhaus T, Aziza J, Bieth E, Laurent N, Bouton JM, Feuillet F, Makni S, Ben Amar H, Laube G, Delezoide AL, Bouvier R, Dijoud F, Ollagnon-Roman E, Roume J, Joubert M, Antignac C, Gubler MC. Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet. 2005 Sep;37(9):964-8. Epub 2005 Aug 14. PMID:16116425 doi:ng1623
↑ Zivna M, Hulkova H, Matignon M, Hodanova K, Vylet'al P, Kalbacova M, Baresova V, Sikora J, Blazkova H, Zivny J, Ivanek R, Stranecky V, Sovova J, Claes K, Lerut E, Fryns JP, Hart PS, Hart TC, Adams JN, Pawtowski A, Clemessy M, Gasc JM, Gubler MC, Antignac C, Elleder M, Kapp K, Grimbert P, Bleyer AJ, Kmoch S. Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure. Am J Hum Genet. 2009 Aug;85(2):204-13. Epub 2009 Aug 6. PMID:19664745 doi:10.1016/j.ajhg.2009.07.010
↑ Tong L, Pav S, Lamarre D, Simoneau B, Lavallee P, Jung G. Crystallographic studies on the binding modes of P2-P3 butanediamide renin inhibitors. J Biol Chem. 1995 Dec 8;270(49):29520-4. PMID:7493993

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Gribouval O, Gonzales M, Neuhaus T, Aziza J, Bieth E, Laurent N, Bouton JM, Feuillet F, Makni S, Ben Amar H, Laube G, Delezoide AL, Bouvier R, Dijoud F, Ollagnon-Roman E, Roume J, Joubert M, Antignac C, Gubler MC. Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet. 2005 Sep;37(9):964-8. Epub 2005 Aug 14. PMID:16116425 doi:ng1623

[2] Zivna M, Hulkova H, Matignon M, Hodanova K, Vylet'al P, Kalbacova M, Baresova V, Sikora J, Blazkova H, Zivny J, Ivanek R, Stranecky V, Sovova J, Claes K, Lerut E, Fryns JP, Hart PS, Hart TC, Adams JN, Pawtowski A, Clemessy M, Gasc JM, Gubler MC, Antignac C, Elleder M, Kapp K, Grimbert P, Bleyer AJ, Kmoch S. Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure. Am J Hum Genet. 2009 Aug;85(2):204-13. Epub 2009 Aug 6. PMID:19664745 doi:10.1016/j.ajhg.2009.07.010

[3] Tong L, Pav S, Lamarre D, Simoneau B, Lavallee P, Jung G. Crystallographic studies on the binding modes of P2-P3 butanediamide renin inhibitors. J Biol Chem. 1995 Dec 8;270(49):29520-4. PMID:7493993

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
 ==CRYSTALLOGRAPHIC STUDIES ON THE BINDING MODES OF P2-P3 BUTANEDIAMIDE RENIN INHIBITORS==
-<StructureSection load='1bil' size='340' side='right' caption='[[1bil]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='1bil' size='340' side='right'caption='[[1bil]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1bil]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BIL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BIL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1bil]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BIL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BIL FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0IU:(2S)-2-[(2-AMINO-1,3-THIAZOL-4-YL)METHYL]-N~1~-[(1S,2R,3R)-1-(CYCLOHEXYLMETHYL)-2,3-DIHYDROXY-5-METHYLHEXYL]-N~4~-[2-(DIMETHYLAMINO)-2-OXOETHYL]-N~4~-[(1S)-1-PHENYLETHYL]BUTANEDIAMIDE'>0IU</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CMV IE-HUMAN PREPRORENIN CDNA, REN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0IU:(2S)-2-[(2-AMINO-1,3-THIAZOL-4-YL)METHYL]-N~1~-[(1S,2R,3R)-1-(CYCLOHEXYLMETHYL)-2,3-DIHYDROXY-5-METHYLHEXYL]-N~4~-[2-(DIMETHYLAMINO)-2-OXOETHYL]-N~4~-[(1S)-1-PHENYLETHYL]BUTANEDIAMIDE'>0IU</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Renin Renin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.15 3.4.23.15] </span></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=1bil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bil OCA], [https://pdbe.org/1bil PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bil RCSB], [https://www.ebi.ac.uk/pdbsum/1bil PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bil ProSAT]</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=1bil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bil OCA], [http://pdbe.org/1bil PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1bil RCSB], [http://www.ebi.ac.uk/pdbsum/1bil PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1bil ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN]] Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:[http://omim.org/entry/267430 267430]]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).<ref>PMID:16116425</ref>   Defects in REN are the cause of familial juvenile hyperuricemic nephropathy type 2 (HNFJ2) [MIM:[http://omim.org/entry/613092 613092]]. It is a renal disease characterized by juvenile onset of hyperuricemia, slowly progressive renal failure and anemia.<ref>PMID:19664745</ref>
+[https://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN] Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:[https://omim.org/entry/267430 267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).<ref>PMID:16116425</ref>   Defects in REN are the cause of familial juvenile hyperuricemic nephropathy type 2 (HNFJ2) [MIM:[https://omim.org/entry/613092 613092]. It is a renal disease characterized by juvenile onset of hyperuricemia, slowly progressive renal failure and anemia.<ref>PMID:19664745</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN]] Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.
+[https://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN] Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.
 == 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/bi/1bil_consurf.spt"</scriptWhenChecked>
+     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bi/1bil_consurf.spt"</scriptWhenChecked>
-     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
    </jmolCheckbox>
@@ Line 32: / Line 31: @@
 </div>
 <div class="pdbe-citations 1bil" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Renin|Renin]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Renin]]
+[[Category: Large Structures]]
-[[Category: Tong, L]]
+[[Category: Tong L]]
-[[Category: Aspartic proteinase]]
-[[Category: Aspartyl protease]]
-[[Category: Cleavage on pair of basic residue]]
-[[Category: Disease mutation]]
-[[Category: Disulfide bond]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Membrane]]
-[[Category: Protease]]
-[[Category: Secreted]]
-[[Category: Zymogen]]

1bil: Difference between revisions

Latest revision as of 04:24, 17 October 2024

CRYSTALLOGRAPHIC STUDIES ON THE BINDING MODES OF P2-P3 BUTANEDIAMIDE RENIN INHIBITORS

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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