1f29

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE ANALYSIS OF CRUZAIN BOUND TO A VINYL SULFONE DERIVED INHIBITOR (I)

Structural highlights

1f29 is a 3 chain structure with sequence from Trypanosoma cruzi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.15Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CYSP_TRYCR Hydrolyzes chromogenic peptides at the carboxyl Arg or Lys; requires at least one more amino acid, preferably Arg, Phe, Val or Leu, between the terminal Arg or Lys and the amino-blocking group. The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle.

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

BACKGROUND: Cysteine proteases of the papain superfamily are present in nearly all groups of eukaryotes and play vital roles in a wide range of biological processes and diseases, including antigen and hormone processing, bacterial infection, arthritis, osteoporosis, Alzheimer's disease and cancer-cell invasion. Because they are critical to the life-cycle progression of many pathogenic protozoa, they represent potential targets for selective inhibitors. Chagas' disease, the leading cause of death due to heart disease in Latin American countries, is transmitted by Trypanosoma cruzi. Cruzain is the major cysteine protease of T cruzi and has been the target of extensive structure-based drug design. RESULTS: High-resolution crystal structures of cruzain bound to a series of potent phenyl-containing vinyl-sulfone, sulfonate and sulfonamide inhibitors have been determined. The structures show a consistent mode of interaction for this family of inhibitors based on a covalent Michael addition formed at the enzyme's active-site cysteine, hydrophobic interactions in the S2 substrate-binding pocket and a strong constellation of hydrogen bonding in the S1' region. CONCLUSIONS: The series of vinyl-sulfone-based inhibitors examined in complex with cruzain was designed to probe recognition and binding potential of an aromatic-rich region of the enzyme. Analysis of the interactions formed shows that aromatic interactions play a less significant role, whereas the strength and importance of hydrogen bonding in the conformation adopted by the inhibitor upon binding to the enzyme was highlighted. A derivative of one inhibitor examined is currently under development as a therapeutic agent against Chagas' disease.

A target within the target: probing cruzain's P1' site to define structural determinants for the Chagas' disease protease.,Brinen LS, Hansell E, Cheng J, Roush WR, McKerrow JH, Fletterick RJ Structure. 2000 Aug 15;8(8):831-40. PMID:10997902^[1]

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

References

↑ Brinen LS, Hansell E, Cheng J, Roush WR, McKerrow JH, Fletterick RJ. A target within the target: probing cruzain's P1' site to define structural determinants for the Chagas' disease protease. Structure. 2000 Aug 15;8(8):831-40. PMID:10997902

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/1f29"

@@ Line 3: / Line 3: @@
 <StructureSection load='1f29' size='340' side='right'caption='[[1f29]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1f29]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Trycr Trycr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F29 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1f29]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F29 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VS1:3-[[N-[MORPHOLIN-N-YL]-CARBONYL]-PHENYLALANINYL-AMINO]-5-+PHENYL-PENTANE-1-SULFONYLBENZENE'>VS1</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]] 2.15&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1f2a|1f2a]], [[1f2b|1f2b]], [[1f2c|1f2c]], [[1aim|1aim]], [[2aim|2aim]], [[1ewl|1ewl]], [[1ewm|1ewm]], [[1ewo|1ewo]], [[1ewp|1ewp]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VS1:3-[[N-[MORPHOLIN-N-YL]-CARBONYL]-PHENYLALANINYL-AMINO]-5-+PHENYL-PENTANE-1-SULFONYLBENZENE'>VS1</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=1f29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f29 OCA], [https://pdbe.org/1f29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f29 RCSB], [https://www.ebi.ac.uk/pdbsum/1f29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f29 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/CYSP_TRYCR CYSP_TRYCR]] Hydrolyzes chromogenic peptides at the carboxyl Arg or Lys; requires at least one more amino acid, preferably Arg, Phe, Val or Leu, between the terminal Arg or Lys and the amino-blocking group.  The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle.
+[https://www.uniprot.org/uniprot/CYSP_TRYCR CYSP_TRYCR] Hydrolyzes chromogenic peptides at the carboxyl Arg or Lys; requires at least one more amino acid, preferably Arg, Phe, Val or Leu, between the terminal Arg or Lys and the amino-blocking group.  The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 15: / Line 15: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f2/1f29_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 37: / Line 37: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Trycr]]
+[[Category: Trypanosoma cruzi]]
-[[Category: Brinen, L S]]
+[[Category: Brinen LS]]
-[[Category: Fletterick, R J]]
+[[Category: Fletterick RJ]]
-[[Category: Hansell, E]]
+[[Category: Hansell E]]
-[[Category: McKerrow, J H]]
+[[Category: McKerrow JH]]
-[[Category: Roush, W R]]
+[[Category: Roush WR]]
-[[Category: Covalent inhibitor]]
-[[Category: Cysteine protease]]
-[[Category: Hydrolase]]
-[[Category: P1' pocket]]
-[[Category: Vinyl sulfone derived]]

1f29

From Proteopedia

Current revision

CRYSTAL STRUCTURE ANALYSIS OF CRUZAIN BOUND TO A VINYL SULFONE DERIVED INHIBITOR (I)

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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