1ur9

Interactions of a family 18 chitinase with the designed inhibitor HM508, and its degradation product, chitobiono-delta-lactone

spinqualitylabelsall models 1ur9, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1ur9 is a 2 chain structure with sequence from Serratia marcescens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: GDL, GOL, NAG, PHJ, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q54276_SERMA 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 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Chitinase 3D structures

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