3bpm: Difference between revisions

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{{Seed}}
[[Image:3bpm.png|left|200px]]


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==Crystal Structure of Falcipain-3 with Its inhibitor, Leupeptin==
The line below this paragraph, containing "STRUCTURE_3bpm", creates the "Structure Box" on the page.
<StructureSection load='3bpm' size='340' side='right'caption='[[3bpm]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[3bpm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] and [https://en.wikipedia.org/wiki/Streptomyces_roseus Streptomyces roseus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BPM FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=AR7:AMINO{[(4S)-4-AMINO-5,5-DIHYDROXYPENTYL]AMINO}METHANIMINIUM'>AR7</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
{{STRUCTURE_3bpm|  PDB=3bpm  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bpm OCA], [https://pdbe.org/3bpm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bpm RCSB], [https://www.ebi.ac.uk/pdbsum/3bpm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bpm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FPC3_PLAF7 FPC3_PLAF7] Cysteine protease which cleaves native host hemoglobin and globin in the food vacuole during the asexual blood stage (PubMed:11716777, PubMed:19357776). Preferentially cleaves substrates which have an arginine at the P1 position and a leucine at the P2 position (PubMed:19357776).<ref>PMID:11716777</ref> <ref>PMID:19357776</ref>
== 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/bp/3bpm_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=3bpm ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Falcipain-2 and falcipain-3 are critical hemoglobinases of Plasmodium falciparum, the most virulent human malaria parasite. We have determined the 2.9 A crystal structure of falcipain-2 in complex with the epoxysuccinate E64 and the 2.5 A crystal structure of falcipain-3 in complex with the aldehyde leupeptin. These complexes represent the first crystal structures of plasmodial cysteine proteases with small molecule inhibitors and the first reported crystal structure of falcipain-3. Our structural analyses indicate that the relative shape and flexibility of the S2 pocket are affected by a number of discrete amino acid substitutions. The cumulative effect of subtle differences, including those at "gatekeeper" positions, may explain the observed kinetic differences between these two closely related enzymes.


===Crystal Structure of Falcipain-3 with Its inhibitor, Leupeptin===
Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity.,Kerr ID, Lee JH, Pandey KC, Harrison A, Sajid M, Rosenthal PJ, Brinen LS J Med Chem. 2009 Feb 12;52(3):852-7. PMID:19128015<ref>PMID:19128015</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3bpm" style="background-color:#fffaf0;"></div>
(as it appears on PubMed at http://www.pubmed.gov), where 19128015 is the PubMed ID number.
== References ==
-->
<references/>
{{ABSTRACT_PUBMED_19128015}}
__TOC__
 
</StructureSection>
==About this Structure==
[[Category: Large Structures]]
3BPM is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BPM OCA].
 
==Reference==
<ref group="xtra">PMID:19128015</ref><references group="xtra"/>
[[Category: Plasmodium falciparum]]
[[Category: Plasmodium falciparum]]
[[Category: Brinen, L S.]]
[[Category: Streptomyces roseus]]
[[Category: Lee, J H.]]
[[Category: Brinen LS]]
[[Category: Kerr, I D.]]
[[Category: Lee JH]]
[[Category: Crystal structure]]
[[Category: Kerr ID]]
[[Category: Cysteine protease]]
[[Category: Falcipain]]
[[Category: Hydrolase]]
[[Category: Malaria]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 22 10:28:45 2009''

Latest revision as of 04:38, 21 November 2024

Crystal Structure of Falcipain-3 with Its inhibitor, LeupeptinCrystal Structure of Falcipain-3 with Its inhibitor, Leupeptin

Structural highlights

3bpm is a 4 chain structure with sequence from Plasmodium falciparum and Streptomyces roseus. 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

FPC3_PLAF7 Cysteine protease which cleaves native host hemoglobin and globin in the food vacuole during the asexual blood stage (PubMed:11716777, PubMed:19357776). Preferentially cleaves substrates which have an arginine at the P1 position and a leucine at the P2 position (PubMed:19357776).[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

Falcipain-2 and falcipain-3 are critical hemoglobinases of Plasmodium falciparum, the most virulent human malaria parasite. We have determined the 2.9 A crystal structure of falcipain-2 in complex with the epoxysuccinate E64 and the 2.5 A crystal structure of falcipain-3 in complex with the aldehyde leupeptin. These complexes represent the first crystal structures of plasmodial cysteine proteases with small molecule inhibitors and the first reported crystal structure of falcipain-3. Our structural analyses indicate that the relative shape and flexibility of the S2 pocket are affected by a number of discrete amino acid substitutions. The cumulative effect of subtle differences, including those at "gatekeeper" positions, may explain the observed kinetic differences between these two closely related enzymes.

Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity.,Kerr ID, Lee JH, Pandey KC, Harrison A, Sajid M, Rosenthal PJ, Brinen LS J Med Chem. 2009 Feb 12;52(3):852-7. PMID:19128015[3]

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

References

  1. ↑ Sijwali PS, Shenai BR, Gut J, Singh A, Rosenthal PJ. Expression and characterization of the Plasmodium falciparum haemoglobinase falcipain-3. Biochem J. 2001 Dec 1;360(Pt 2):481-9. PMID:11716777 doi:10.1042/0264-6021:3600481
  2. ↑ Subramanian S, Hardt M, Choe Y, Niles RK, Johansen EB, Legac J, Gut J, Kerr ID, Craik CS, Rosenthal PJ. Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3. PLoS One. 2009;4(4):e5156. PMID:19357776 doi:10.1371/journal.pone.0005156
  3. ↑ Kerr ID, Lee JH, Pandey KC, Harrison A, Sajid M, Rosenthal PJ, Brinen LS. Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity. J Med Chem. 2009 Feb 12;52(3):852-7. PMID:19128015 doi:10.1021/jm8013663

3bpm, resolution 2.50Å

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