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1bmq

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CRYSTAL STRUCTURE OF THE COMPLEX OF INTERLEUKIN-1BETA CONVERTING ENZYME (ICE) WITH A PEPTIDE BASED INHIBITOR, (3S )-N-METHANESULFONYL-3-({1-[N-(2-NAPHTOYL)-L-VALYL]-L-PROLYL }AMINO)-4-OXOBUTANAMIDE

Structural highlights

1bmq 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 2.5Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CASP1_HUMAN Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis.^[1] ^[2]

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

Based on the X-ray structure of the complex of Ac-Tyr-Val-Ala-Asp-H (L-709049) and interleukin-1 beta converting enzyme (ICE), we synthesized compounds which were derived from 2-NapCO-Val-Pro-Asp-CH2OPh (1) to obtain a potent inhibitor in the cell assay. Among these compounds, (3S)-N-methanesulfonyl-3-[[1-[N-(2-naphthoyl)-L-valyl]-L-prolyl]amino]- 4-oxobutanamide (27c) showed high potency not only in the enzyme assay but also cell assay with IC50 values of 38 nM and 0.23 microM, respectively. Compound 27c, with a c log P value of 1.76, had a more hydrophilic character compared with 1. Compound 27c also dose dependently inhibited LPS-primed ATP-induced IL-1 beta release in mice. The crystal structure of the complex of compound 27c and ICE revealed that compound 27c had further interactions with ICE in the naphthoyl group at the P4 position and in the methyl group of the methanesulfonamidecarbonyl group at the P1 position, compared with L-709049. To our knowledge, compound 27c is the first example that shows a strong inhibitory activity without the carboxyl group at the P1 position.

Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex.,Okamoto Y, Anan H, Nakai E, Morihira K, Yonetoku Y, Kurihara H, Sakashita H, Terai Y, Takeuchi M, Shibanuma T, Isomura Y Chem Pharm Bull (Tokyo). 1999 Jan;47(1):11-21. PMID:9987822^[3]

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

References

↑ Alnemri ES, Fernandes-Alnemri T, Litwack G. Cloning and expression of four novel isoforms of human interleukin-1 beta converting enzyme with different apoptotic activities. J Biol Chem. 1995 Mar 3;270(9):4312-7. PMID:7876192
↑ Feng Q, Li P, Leung PC, Auersperg N. Caspase-1zeta, a new splice variant of the caspase-1 gene. Genomics. 2004 Sep;84(3):587-91. PMID:15498465 doi:http://dx.doi.org/S0888-7543(04)00161-2
↑ Okamoto Y, Anan H, Nakai E, Morihira K, Yonetoku Y, Kurihara H, Sakashita H, Terai Y, Takeuchi M, Shibanuma T, Isomura Y. Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex. Chem Pharm Bull (Tokyo). 1999 Jan;47(1):11-21. PMID:9987822

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1bmq"

@@ Line 3: / Line 3: @@
 <StructureSection load='1bmq' size='340' side='right'caption='[[1bmq]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1bmq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BMQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BMQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1bmq]] 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=1BMQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BMQ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MNO:(3S)-N-METHANESULFONYL-3-({1-[N-(2-NAPHTOYL)-L-VALYL]-L-PROLYL}AMINO)-4-OXOBUTANAMIDE'>MNO</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]] 2.5&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Caspase-1 Caspase-1], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.36 3.4.22.36] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MNO:(3S)-N-METHANESULFONYL-3-({1-[N-(2-NAPHTOYL)-L-VALYL]-L-PROLYL}AMINO)-4-OXOBUTANAMIDE'>MNO</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=1bmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bmq OCA], [https://pdbe.org/1bmq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bmq RCSB], [https://www.ebi.ac.uk/pdbsum/1bmq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bmq ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/CASP1_HUMAN CASP1_HUMAN]] Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis.<ref>PMID:7876192</ref> <ref>PMID:15498465</ref>
+[https://www.uniprot.org/uniprot/CASP1_HUMAN CASP1_HUMAN] Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis.<ref>PMID:7876192</ref> <ref>PMID:15498465</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 36: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Caspase-1]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Anan, H]]
+[[Category: Anan H]]
-[[Category: Isomura, Y]]
+[[Category: Isomura Y]]
-[[Category: Katayama, N]]
+[[Category: Katayama N]]
-[[Category: Kurihara, H]]
+[[Category: Kurihara H]]
-[[Category: Morihira, K]]
+[[Category: Morihira K]]
-[[Category: Nakai, E]]
+[[Category: Nakai E]]
-[[Category: Okamoto, Y]]
+[[Category: Okamoto Y]]
-[[Category: Sakashita, H]]
+[[Category: Sakashita H]]
-[[Category: Shibanuma, T]]
+[[Category: Shibanuma T]]
-[[Category: Takeuchi, M]]
+[[Category: Takeuchi M]]
-[[Category: Terai, Y]]
+[[Category: Terai Y]]
-[[Category: Yonetoku, Y]]
+[[Category: Yonetoku Y]]
-[[Category: Caspase]]
-[[Category: Hydrolase]]

1bmq

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF THE COMPLEX OF INTERLEUKIN-1BETA CONVERTING ENZYME (ICE) WITH A PEPTIDE BASED INHIBITOR, (3S )-N-METHANESULFONYL-3-({1-[N-(2-NAPHTOYL)-L-VALYL]-L-PROLYL }AMINO)-4-OXOBUTANAMIDE

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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