1ur9: Difference between revisions
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'''INTERACTIONS OF A FAMILY 18 CHITINASE WITH THE DESIGNED INHIBITOR HM508, AND ITS DEGRADATION PRODUCT, CHITOBIONO-DELTA-LACTONE''' | {{Structure | ||
|PDB= 1ur9 |SIZE=350|CAPTION= <scene name='initialview01'>1ur9</scene>, resolution 1.80Å | |||
|SITE= <scene name='pdbsite=GLU:Phj+Binding+Site+For+Chain+B'>GLU</scene> | |||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=GDL:2-ACETAMIDO-2-DEOXY-D-GLUCONO-1,5-LACTONE'>GDL</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Chitinase Chitinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.14 3.2.1.14] | |||
|GENE= | |||
}} | |||
'''INTERACTIONS OF A FAMILY 18 CHITINASE WITH THE DESIGNED INHIBITOR HM508, AND ITS DEGRADATION PRODUCT, CHITOBIONO-DELTA-LACTONE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1UR9 is a [ | 1UR9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Serratia_marcescens Serratia marcescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UR9 OCA]. | ||
==Reference== | ==Reference== | ||
Interactions of a family 18 chitinase with the designed inhibitor HM508 and its degradation product, chitobiono-delta-lactone., Vaaje-Kolstad G, Vasella A, Peter MG, Netter C, Houston DR, Westereng B, Synstad B, Eijsink VG, van Aalten DM, J Biol Chem. 2004 Jan 30;279(5):3612-9. Epub 2003 Nov 3. PMID:[http:// | Interactions of a family 18 chitinase with the designed inhibitor HM508 and its degradation product, chitobiono-delta-lactone., Vaaje-Kolstad G, Vasella A, Peter MG, Netter C, Houston DR, Westereng B, Synstad B, Eijsink VG, van Aalten DM, J Biol Chem. 2004 Jan 30;279(5):3612-9. Epub 2003 Nov 3. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14597613 14597613] | ||
[[Category: Chitinase]] | [[Category: Chitinase]] | ||
[[Category: Serratia marcescens]] | [[Category: Serratia marcescens]] | ||
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[[Category: lactone]] | [[Category: lactone]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:35:39 2008'' | ||
Revision as of 15:35, 20 March 2008
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| , resolution 1.80Å | |||||||
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| Sites: | |||||||
| Ligands: | , , and | ||||||
| Activity: | Chitinase, with EC number 3.2.1.14 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
INTERACTIONS OF A FAMILY 18 CHITINASE WITH THE DESIGNED INHIBITOR HM508, AND ITS DEGRADATION PRODUCT, CHITOBIONO-DELTA-LACTONE
OverviewOverview
We describe enzymological and structural analyses of the interaction between the family 18 chitinase ChiB from Serratia marcescens and the designed inhibitor N,N'-diacetylchitobionoxime-N-phenylcarbamate (HM508). HM508 acts as a competitive inhibitor of this enzyme with a K(i) in the 50 microM range. Active site mutants of ChiB show K(i) values ranging from 1 to 200 microM, providing insight into some of the interactions that determine inhibitor affinity. Interestingly, the wild type enzyme slowly degrades HM508, but the inhibitor is essentially stable in the presence of the moderately active D142N mutant of ChiB. The crystal structure of the D142N-HM508 complex revealed that the two sugar moieties bind to the -2 and -1 subsites, whereas the phenyl group interacts with aromatic side chains that line the +1 and +2 subsites. Enzymatic degradation of HM508, as well as a Trp --> Ala mutation in the +2 subsite of ChiB, led to reduced affinity for the inhibitor, showing that interactions between the phenyl group and the enzyme contribute to binding. Interestingly, a complex of enzymatically degraded HM508 with the wild type enzyme showed a chitobiono-delta-lactone bound in the -2 and -1 subsites, despite the fact that the equilibrium between the lactone and the hydroxy acid forms in solution lies far toward the latter. This shows that the active site preferentially binds the (4)E conformation of the -1 sugar, which resembles the proposed transition state of the reaction.
About this StructureAbout this Structure
1UR9 is a Single protein structure of sequence from Serratia marcescens. Full crystallographic information is available from OCA.
ReferenceReference
Interactions of a family 18 chitinase with the designed inhibitor HM508 and its degradation product, chitobiono-delta-lactone., Vaaje-Kolstad G, Vasella A, Peter MG, Netter C, Houston DR, Westereng B, Synstad B, Eijsink VG, van Aalten DM, J Biol Chem. 2004 Jan 30;279(5):3612-9. Epub 2003 Nov 3. PMID:14597613
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