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| - | [[Image:1av7.gif|left|200px]] | |
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| - | <!-- | + | ==SUBTILISIN CARLSBERG L-NAPHTHYL-1-ACETAMIDO BORONIC ACID INHIBITOR COMPLEX== |
| - | The line below this paragraph, containing "STRUCTURE_1av7", creates the "Structure Box" on the page.
| + | <StructureSection load='1av7' size='340' side='right'caption='[[1av7]], [[Resolution|resolution]] 2.60Å' 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'>[[1av7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AV7 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]] 2.6Å</td></tr> |
| - | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SBL:L-NAPHTHYL-1-ACETAMIDO+BORONIC+ACID+ALANINE'>SBL</scene></td></tr> |
| - | {{STRUCTURE_1av7| PDB=1av7 | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1av7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1av7 OCA], [https://pdbe.org/1av7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1av7 RCSB], [https://www.ebi.ac.uk/pdbsum/1av7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1av7 ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SUBC_BACLI SUBC_BACLI] Subtilisin is an extracellular alkaline serine protease, it catalyzes the hydrolysis of proteins and peptide amides (Ref.4, PubMed:11109488). Shows high specificity for aromatic and hydrophobic amino acids in the P1 substrate position (PubMed:11109488). May play an important role in the degradation of feather keratin (PubMed:11109488).<ref>PMID:11109488</ref> <ref>PMID:4967581</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/av/1av7_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=1av7 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | In order to probe the structural basis of stereoselectivity in the serine protease family, a series of enantiomeric boronic acids RCH2CH(NHCOCH3)B(OH)2 has been synthesized and kinetically characterized as transition-state analog inhibitors using alpha-chymotrypsin and subtilisin Carlsberg as model systems. When the R-substituent in this series was changed from a p-chlorophenyl to a 1-naphthyl group, alpha-chymotrypsin, but not subtilisin, reversed its usual preference for l-enantiomers and bound more tightly to the D-enantiomer [Martichonok, V., & Jones, J. B. (1996) J. Am. Chem. Soc. 118, 950-958]. The structural factors responsible for the differences in stereoselectivity between the two enzymes have been explored by X-ray crystallographic examination of subtilisin Carlsberg and gamma-chymotrypsin complexes of the L- and D-enantiomers of p-chlorophenyl and 1-naphthyl boronic acid derivatives. In both enzymes, the L-isomers of the inhibitors, which are more closely related to the natural L-amino acid substrates, form tetrahedral adducts, covalently linking the central boron atom and Ogamma of the catalytic serine. The d-isomers, however, differ in the way they interact with subtilisin or gamma-chymotrypsin. With subtilisin, both the D-p-chlorophenyl and D-1-naphthyl inhibitor complexes form covalent Ser Ogamma-to-boron bonds, but with gamma-chymotrypsin, the same inhibitors lead to novel tetrahedral adducts covalently linking both Ser195 Ogamma and His57 Nepsilon2 covalently via the boron atom. |
| | | | |
| - | '''SUBTILISIN CARLSBERG L-NAPHTHYL-1-ACETAMIDO BORONIC ACID INHIBITOR COMPLEX'''
| + | Differences in binding modes of enantiomers of 1-acetamido boronic acid based protease inhibitors: crystal structures of gamma-chymotrypsin and subtilisin Carlsberg complexes.,Stoll VS, Eger BT, Hynes RC, Martichonok V, Jones JB, Pai EF Biochemistry. 1998 Jan 13;37(2):451-62. PMID:9425066<ref>PMID:9425066</ref> |
| - | | + | |
| - | | + | |
| - | ==Overview==
| + | |
| - | In order to probe the structural basis of stereoselectivity in the serine protease family, a series of enantiomeric boronic acids RCH2CH(NHCOCH3)B(OH)2 has been synthesized and kinetically characterized as transition-state analog inhibitors using alpha-chymotrypsin and subtilisin Carlsberg as model systems. When the R-substituent in this series was changed from a p-chlorophenyl to a 1-naphthyl group, alpha-chymotrypsin, but not subtilisin, reversed its usual preference for l-enantiomers and bound more tightly to the D-enantiomer [Martichonok, V., & Jones, J. B. (1996) J. Am. Chem. Soc. 118, 950-958]. The structural factors responsible for the differences in stereoselectivity between the two enzymes have been explored by X-ray crystallographic examination of subtilisin Carlsberg and gamma-chymotrypsin complexes of the L- and D-enantiomers of p-chlorophenyl and 1-naphthyl boronic acid derivatives. In both enzymes, the L-isomers of the inhibitors, which are more closely related to the natural L-amino acid substrates, form tetrahedral adducts, covalently linking the central boron atom and Ogamma of the catalytic serine. The d-isomers, however, differ in the way they interact with subtilisin or gamma-chymotrypsin. With subtilisin, both the D-p-chlorophenyl and D-1-naphthyl inhibitor complexes form covalent Ser Ogamma-to-boron bonds, but with gamma-chymotrypsin, the same inhibitors lead to novel tetrahedral adducts covalently linking both Ser195 Ogamma and His57 Nepsilon2 covalently via the boron atom.
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1AV7 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AV7 OCA].
| + | </div> |
| | + | <div class="pdbe-citations 1av7" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | Differences in binding modes of enantiomers of 1-acetamido boronic acid based protease inhibitors: crystal structures of gamma-chymotrypsin and subtilisin Carlsberg complexes., Stoll VS, Eger BT, Hynes RC, Martichonok V, Jones JB, Pai EF, Biochemistry. 1998 Jan 13;37(2):451-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9425066 9425066]
| + | *[[Subtilisin 3D structures|Subtilisin 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Bacillus licheniformis]] | | [[Category: Bacillus licheniformis]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Subtilisin]]
| + | [[Category: Eger BT]] |
| - | [[Category: Eger, B T.]] | + | [[Category: Hynes RC]] |
| - | [[Category: Hynes, R C.]] | + | [[Category: Jones JB]] |
| - | [[Category: Jones, J B.]] | + | [[Category: Martichonok V]] |
| - | [[Category: Martichonok, V.]] | + | [[Category: Pai EF]] |
| - | [[Category: Pai, E F.]] | + | [[Category: Stoll VS]] |
| - | [[Category: Stoll, V S.]] | + | |
| - | [[Category: Boronic acid inhibitor]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:43:57 2008''
| + | |
| Structural highlights
Function
SUBC_BACLI Subtilisin is an extracellular alkaline serine protease, it catalyzes the hydrolysis of proteins and peptide amides (Ref.4, PubMed:11109488). Shows high specificity for aromatic and hydrophobic amino acids in the P1 substrate position (PubMed:11109488). May play an important role in the degradation of feather keratin (PubMed:11109488).[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
In order to probe the structural basis of stereoselectivity in the serine protease family, a series of enantiomeric boronic acids RCH2CH(NHCOCH3)B(OH)2 has been synthesized and kinetically characterized as transition-state analog inhibitors using alpha-chymotrypsin and subtilisin Carlsberg as model systems. When the R-substituent in this series was changed from a p-chlorophenyl to a 1-naphthyl group, alpha-chymotrypsin, but not subtilisin, reversed its usual preference for l-enantiomers and bound more tightly to the D-enantiomer [Martichonok, V., & Jones, J. B. (1996) J. Am. Chem. Soc. 118, 950-958]. The structural factors responsible for the differences in stereoselectivity between the two enzymes have been explored by X-ray crystallographic examination of subtilisin Carlsberg and gamma-chymotrypsin complexes of the L- and D-enantiomers of p-chlorophenyl and 1-naphthyl boronic acid derivatives. In both enzymes, the L-isomers of the inhibitors, which are more closely related to the natural L-amino acid substrates, form tetrahedral adducts, covalently linking the central boron atom and Ogamma of the catalytic serine. The d-isomers, however, differ in the way they interact with subtilisin or gamma-chymotrypsin. With subtilisin, both the D-p-chlorophenyl and D-1-naphthyl inhibitor complexes form covalent Ser Ogamma-to-boron bonds, but with gamma-chymotrypsin, the same inhibitors lead to novel tetrahedral adducts covalently linking both Ser195 Ogamma and His57 Nepsilon2 covalently via the boron atom.
Differences in binding modes of enantiomers of 1-acetamido boronic acid based protease inhibitors: crystal structures of gamma-chymotrypsin and subtilisin Carlsberg complexes.,Stoll VS, Eger BT, Hynes RC, Martichonok V, Jones JB, Pai EF Biochemistry. 1998 Jan 13;37(2):451-62. PMID:9425066[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Evans KL, Crowder J, Miller ES. Subtilisins of Bacillus spp. hydrolyze keratin and allow growth on feathers. Can J Microbiol. 2000 Nov;46(11):1004-11. doi: 10.1139/w00-085. PMID:11109488 doi:http://dx.doi.org/10.1139/w00-085
- ↑ Smith EL, DeLange RJ, Evans WH, Landon M, Markland FS. Subtilisin Carlsberg. V. The complete sequence; comparison with subtilisin BPN'; evolutionary relationships. J Biol Chem. 1968 May 10;243(9):2184-91. PMID:4967581
- ↑ Stoll VS, Eger BT, Hynes RC, Martichonok V, Jones JB, Pai EF. Differences in binding modes of enantiomers of 1-acetamido boronic acid based protease inhibitors: crystal structures of gamma-chymotrypsin and subtilisin Carlsberg complexes. Biochemistry. 1998 Jan 13;37(2):451-62. PMID:9425066 doi:http://dx.doi.org/10.1021/bi971166o
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