3a2y

E. coli Gsp amidase C59A complexed with Gsp

spinqualitylabelsall models 3a2y, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3a2y is a 1 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: TS5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GSP_ECOLI Catalyzes the formation of an amide bond between glutathione and spermidine coupled with hydrolysis of ATP; also catalyzes the hydrolysis of glutathionylspermidine to glutathione and spermidine. 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 The bifunctional Escherichia coli glutathionylspermidine synthetase/amidase (GspSA), catalyzes both the synthesis and hydrolysis of Gsp. Its amidase domain (GspA), which catalyzes the hydrolysis of Gsp into glutathione and spermidine, plays an important role in redox sensing and protein S-thiolation. To gain insight of the regulation and catalytic mechanism of GspA and further understand the recycling of the Gsp dimer and Gsp-S-protein adducts, we solved two crystal structures of GspA and GspSA both with the C59A mutation and bound with the substrate, Gsp. In both structures, Cys59, His131 and Glu147 form the catalytic triad, which is similar to other cysteine proteases. Comparison of the GspA_Gsp complex and apo GspSA structures indicates that upon binding with Gsp, the side chains of Asn149 and Gln58 of the amidase domain are induced to move closer to the carbonyl oxygen of the cleaved amide bond of Gsp, thereby participating in catalysis. In addition, the helix-loop region of GspA, corresponding to the sequence (30)YSSLDPQEYEDDA(42), involves in regulating the substrate binding. Our previous study indicated that the thiol of Cys59 of GspA is only oxidized to sulfenic acid by H(2)O(2). When comparing the active site of GspA with those of other cysteine proteases, we found that limited space and hydrophobicity of the environment around Cys59 play an important role to inhibit its further oxidation. The structural results presented here not only elucidate the catalytic mechanism and regulation of GspA, but also help us design small molecules to inhibit or probe for the activity of GspA. Structure and mechanism of Escherichia coli glutathionylspermidine amidase belonging to the family of cysteine, histidine-dependent amidohydrolases/peptidases.,Pai CH, Wu HJ, Lin CH, Wang AH Protein Sci. 2011 Jan 11. PMID:21226054 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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