2gpl

From Proteopedia

(Difference between revisions)

Revision as of 00:19, 31 March 2008

, resolution 2.81Å

Ligands:

Gene:

Activity:

Proteasome endopeptidase complex, with EC number 3.4.25.1

Related:

1RYP, 1JD2

Resources:

FirstGlance, OCA, PDBsum, RCSB

Coordinates:

save as pdb, mmCIF, xml

TMC-95 based biphenyl-ether macrocycles: specific proteasome inhibitors

Overview

TMC-95's natural cyclic tripeptide metabolites represent potent competitive proteasome inhibitors. The constrained conformation of TMC-95 proteasomal inhibitors provides the driving force for entropically high-affinity binding. Based on the crystal structure of the proteasome:TMC-95A complex, the synthetically challenging TMC-95 core structure was used for the design and synthesis of less demanding biphenyl-ether macrocycles, in which the biphenyl-ether moiety functions as an endocyclic clamp restricting its tripeptide backbone. These simplified analogs allowed us to identify high plasticity of the proteasomal tryptic-like specificity pocket. Biphenyl-ether compounds extended with an amide group were hydrolyzed by the proteasome, although the crystal structure of such proteasome:biphenyl-ether complexes revealed quenching of proteolysis at the acyl-enzyme intermediate. Our data reveal that biphenyl-ether derivatives bind noncovalently to the proteasomal tryptic-like active site in a reversible substrate-like manner without allosteric changes of active site residues.

About this Structure

2GPL is a Protein complex structure of sequences from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

Reference

TMC-95-based inhibitor design provides evidence for the catalytic versatility of the proteasome., Groll M, Gotz M, Kaiser M, Weyher E, Moroder L, Chem Biol. 2006 Jun;13(6):607-14. PMID:16793518

Page seeded by OCA on Mon Mar 31 03:19:47 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2gpl"

@@ Line 4: / Line 4: @@
 |PDB= 2gpl |SIZE=350|CAPTION= <scene name='initialview01'>2gpl</scene>, resolution 2.81&Aring;
 |SITE=
-|LIGAND= <scene name='pdbligand=BIQ:BENZYL [12-(2-AMINO-2-OXOETHYL)-4-NITRO-10,13-DIOXO-15-[(PROPYLAMINO)CARBONYL]-2-OXA-11,14-DIAZATRICYCLO[15 .2.2.1~3,7~]DOCOSA-1(19),3(22),4,6,17,20-HEXAEN-9-YL]CARBAMATE'>BIQ</scene>
+|LIGAND= <scene name='pdbligand=BIQ:BENZYL+[12-(2-AMINO-2-OXOETHYL)-4-NITRO-10,13-DIOXO-15-[(PROPYLAMINO)CARBONYL]-2-OXA-11,14-DIAZATRICYCLO[15+.2.2.1~3,7~]DOCOSA-1(19),3(22),4,6,17,20-HEXAEN-9-YL]CARBAMATE'>BIQ</scene>
-|ACTIVITY= [http://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex Proteasome endopeptidase complex], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.25.1 3.4.25.1]
+|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex Proteasome endopeptidase complex], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.25.1 3.4.25.1] </span>
 |GENE= PRS4, PRE8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PRE1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PRE2, DOA3, PRG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PRS3, PRE7, PTS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PRE4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PRE3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PRS5, PRE9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PRE6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PUP2, DOA5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PRE5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PRS1, PRC1, PRE10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PRS2, PRC2, SCL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PUP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PUP3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])
+|DOMAIN=
+|RELATEDENTRY=[[1ryp|1RYP]], [[1jd2|1JD2]]
+|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gpl OCA], [http://www.ebi.ac.uk/pdbsum/2gpl PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gpl RCSB]</span>
 }}
@@ Line 28: / Line 31: @@
 [[Category: Moroder, M.]]
 [[Category: Weyher, E.]]
-[[Category: BIQ]]
+[[Category: ntn-hydrolase]]
-[[Category: proteasomal subunit fold represents an antiparallel beta-sheet flanked by helices; ntn-hydrolase]]
+[[Category: proteasomal subunit fold represents an antiparallel beta-sheet flanked by helice]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:07:27 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:19:47 2008''

2gpl

From Proteopedia

Revision as of 00:19, 31 March 2008

Overview

About this Structure

Reference

Proteopedia Page Contributors and Editors (what is this?)

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