1f57: Difference between revisions
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< | ==CARBOXYPEPTIDASE A COMPLEX WITH D-CYSTEINE AT 1.75 A== | ||
<StructureSection load='1f57' size='340' side='right'caption='[[1f57]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1f57]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F57 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F57 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DCY:D-CYSTEINE'>DCY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1f57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f57 OCA], [https://pdbe.org/1f57 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f57 RCSB], [https://www.ebi.ac.uk/pdbsum/1f57 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f57 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CBPA1_BOVIN CBPA1_BOVIN] Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro (By similarity). | |||
== 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/f5/1f57_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1f57 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
D-Cysteine differs from the antiarthritis drug D-penicillamine by only two methyl groups on the beta-carbon yet inhibits carboxypeptidase A (CPD) by a distinct mechanism: D-cysteine binds tightly to the active site zinc, while D-penicillamine catalyzes metal removal. To investigate the structural basis for this difference, we solved the crystal structure of carboxypeptidase A complexed with D-cysteine (D-Cys) at 1.75-A resolution. D-Cys binds the active site zinc with a sulfur ligand and forms additional interactions with surrounding side chains of the enzyme. The structure explains the difference in potency between D-Cys and L-Cys and provides insight into the mechanism of D-penicillamine inhibition. D-Cys binding induces a concerted motion of the side chains around the zinc ion, similar to that found in other carboxypeptidase-inhibitor crystal structures and along a limited path. Analysis of concerted motions of CPD and CPD-inhibitor crystal structures reveals a clustering of these structures into distinct groups. Using the restricted conformational flexibility of a drug target in this type of analysis could greatly enhance efficiency in drug design. | |||
Crystal structure of carboxypeptidase A complexed with D-cysteine at 1.75 A - inhibitor-induced conformational changes.,van Aalten DM, Chong CR, Joshua-Tor L Biochemistry. 2000 Aug 22;39(33):10082-9. PMID:10955996<ref>PMID:10955996</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1f57" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Chong CR]] | |||
[[Category: Joshua-Tor L]] | |||
[[Category: Chong | [[Category: Van Aalten DM]] | ||
[[Category: Joshua-Tor | |||
[[Category: | |||
Latest revision as of 09:02, 9 August 2023
CARBOXYPEPTIDASE A COMPLEX WITH D-CYSTEINE AT 1.75 ACARBOXYPEPTIDASE A COMPLEX WITH D-CYSTEINE AT 1.75 A
Structural highlights
FunctionCBPA1_BOVIN Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro (By similarity). 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 PubMedD-Cysteine differs from the antiarthritis drug D-penicillamine by only two methyl groups on the beta-carbon yet inhibits carboxypeptidase A (CPD) by a distinct mechanism: D-cysteine binds tightly to the active site zinc, while D-penicillamine catalyzes metal removal. To investigate the structural basis for this difference, we solved the crystal structure of carboxypeptidase A complexed with D-cysteine (D-Cys) at 1.75-A resolution. D-Cys binds the active site zinc with a sulfur ligand and forms additional interactions with surrounding side chains of the enzyme. The structure explains the difference in potency between D-Cys and L-Cys and provides insight into the mechanism of D-penicillamine inhibition. D-Cys binding induces a concerted motion of the side chains around the zinc ion, similar to that found in other carboxypeptidase-inhibitor crystal structures and along a limited path. Analysis of concerted motions of CPD and CPD-inhibitor crystal structures reveals a clustering of these structures into distinct groups. Using the restricted conformational flexibility of a drug target in this type of analysis could greatly enhance efficiency in drug design. Crystal structure of carboxypeptidase A complexed with D-cysteine at 1.75 A - inhibitor-induced conformational changes.,van Aalten DM, Chong CR, Joshua-Tor L Biochemistry. 2000 Aug 22;39(33):10082-9. PMID:10955996[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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