1czi: Difference between revisions
New page: left|200px<br /> <applet load="1czi" size="450" color="white" frame="true" align="right" spinBox="true" caption="1czi, resolution 2.30Å" /> '''CHYMOSIN COMPLEX WI... |
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== | ==CHYMOSIN COMPLEX WITH THE INHIBITOR CP-113972== | ||
In the crystal structure of uncomplexed native chymosin, the beta-hairpin | <StructureSection load='1czi' size='340' side='right'caption='[[1czi]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1czi]] is a 2 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=1CZI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CZI 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]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NOR:CYCLOHEXYL-NORSTATINE'>NOR</scene>, <scene name='pdbligand=PHI:IODO-PHENYLALANINE'>PHI</scene>, <scene name='pdbligand=SMC:S-METHYLCYSTEINE'>SMC</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=1czi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1czi OCA], [https://pdbe.org/1czi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1czi RCSB], [https://www.ebi.ac.uk/pdbsum/1czi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1czi ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CHYM_BOVIN CHYM_BOVIN] Chymosin is synthesized in the mucosa of the abomasum (fourth stomach) of young (unweaned) ruminants. The enzyme hydrolyzes casein to paracasein. | |||
== 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/cz/1czi_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=1czi ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In the crystal structure of uncomplexed native chymosin, the beta-hairpin at the active site, known as 'the flap', adopts a different conformation from that of other aspartic proteinases. This conformation would prevent the mode of binding of substrates/inhibitors generally found in other aspartic proteinase complexes. We now report the X-ray analysis of chymosin complexed with a reduced bond inhibitor CP-113972 inverted question mark(2R,3S)-isopropyl 3-[(L-prolyl-p-iodo-L-phenylalanyl-S-methyl-cysteinyl)amino-4]-cyclohexy l-2-hydroxybutanoate inverted question mark at 2.3 A resolution in a novel crystal form of spacegroup R32. The structure has been refined by restrained least-squares methods to a final R-factor of 0.19 for a total of 11 988 independent reflections in the resolution range 10 to 2.3 A. The extended beta-strand conformation of the inhibitor allows hydrogen bonds within the active site, while its sidechains make both electrostatic and hydrophobic interactions with residues lining the specificity pockets S4-->S1. The flap closes over the active site cleft in a way that closely resembles that of other previously determined aspartic proteinase inhibitor complexes. We conclude that the usual position and conformation of the flap found in other aspartic proteinases is available to native chymosin. The conformation observed in the native crystal form may result from intermolecular interactions between symmetry-related molecules in the crystal lattice. | |||
A 2.3 A resolution structure of chymosin complexed with a reduced bond inhibitor shows that the active site beta-hairpin flap is rearranged when compared with the native crystal structure.,Groves MR, Dhanaraj V, Badasso M, Nugent P, Pitts JE, Hoover DJ, Blundell TL Protein Eng. 1998 Oct;11(10):833-40. PMID:9862200<ref>PMID:9862200</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1czi" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Badasso | [[Category: Badasso M]] | ||
[[Category: Blundell | [[Category: Blundell TL]] | ||
[[Category: Dhanaraj | [[Category: Dhanaraj V]] | ||
[[Category: Groves | [[Category: Groves MR]] | ||
[[Category: Hoover | [[Category: Hoover D]] | ||
[[Category: Nugent | [[Category: Nugent P]] | ||
[[Category: Pitts | [[Category: Pitts JE]] | ||
Latest revision as of 08:55, 9 August 2023
CHYMOSIN COMPLEX WITH THE INHIBITOR CP-113972CHYMOSIN COMPLEX WITH THE INHIBITOR CP-113972
Structural highlights
FunctionCHYM_BOVIN Chymosin is synthesized in the mucosa of the abomasum (fourth stomach) of young (unweaned) ruminants. The enzyme hydrolyzes casein to paracasein. 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 PubMedIn the crystal structure of uncomplexed native chymosin, the beta-hairpin at the active site, known as 'the flap', adopts a different conformation from that of other aspartic proteinases. This conformation would prevent the mode of binding of substrates/inhibitors generally found in other aspartic proteinase complexes. We now report the X-ray analysis of chymosin complexed with a reduced bond inhibitor CP-113972 inverted question mark(2R,3S)-isopropyl 3-[(L-prolyl-p-iodo-L-phenylalanyl-S-methyl-cysteinyl)amino-4]-cyclohexy l-2-hydroxybutanoate inverted question mark at 2.3 A resolution in a novel crystal form of spacegroup R32. The structure has been refined by restrained least-squares methods to a final R-factor of 0.19 for a total of 11 988 independent reflections in the resolution range 10 to 2.3 A. The extended beta-strand conformation of the inhibitor allows hydrogen bonds within the active site, while its sidechains make both electrostatic and hydrophobic interactions with residues lining the specificity pockets S4-->S1. The flap closes over the active site cleft in a way that closely resembles that of other previously determined aspartic proteinase inhibitor complexes. We conclude that the usual position and conformation of the flap found in other aspartic proteinases is available to native chymosin. The conformation observed in the native crystal form may result from intermolecular interactions between symmetry-related molecules in the crystal lattice. A 2.3 A resolution structure of chymosin complexed with a reduced bond inhibitor shows that the active site beta-hairpin flap is rearranged when compared with the native crystal structure.,Groves MR, Dhanaraj V, Badasso M, Nugent P, Pitts JE, Hoover DJ, Blundell TL Protein Eng. 1998 Oct;11(10):833-40. PMID:9862200[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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