4lc5 | pdb_00004lc5

Structural basis of substrate specificity of CDA superfamily guanine deaminase

spinqualitylabelsall models 4lc5, resolution 1.97Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4lc5 is a 2 chain structure with sequence from Niteu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 9MG, EDO, ZN Related: 4hrq, 4hrw, 2g84, 4lcn, 4lco, 4lcp, 4ld2, 4ld4 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Guanine deaminases (GDs) are important enzymes involved in purine metabolism as well as nucleotide anabolism pathways that exhibit a high degree of fidelity. Here, the structural basis of the substrate specificity of GDs was investigated by determining a series of X-ray structures of NE0047 (GD from Nitrosomonas europaea) with nucleobase analogues and nucleosides. The structures demonstrated that the interactions in the GD active site are tailor-made to accommodate only guanine and any substitutions in the purine ring or introduction of a pyrimidine ring results in rearrangement of the bases in a catalytically unfavorable orientation, away from the proton shuttling residue E143. In addition, X-ray structural studies performed on cytidine revealed that although it binds in an optimal conformation, its deamination does not occur because of the inability of the enzyme to orchestrate the closure of the catalytically important C-terminal loop (residues 181-189). Isothermal calorimetry measurements established that these nucleoside moieties also disrupt the sequential mode of ligand binding, thereby abrogating all intersubunit communication. Intriguingly, it was recently discovered that GDs can also serve as endogenous ammeline deaminases, although it is structurally nonhomologous with guanine. To understand the mechanism of dual-substrate specificity, the structure of NE0047 in complex with ammeline was determined to a resolution of 2.7 A. The structure revealed that ammeline not only fits in the active site in a catalytically favorable orientation but also allows for closure of the C-terminal loop. Structural basis of the substrate specificity of cytidine deaminase superfamily Guanine deaminase.,Bitra A, Biswas A, Anand R Biochemistry. 2013 Nov 12;52(45):8106-14. doi: 10.1021/bi400818e. Epub 2013 Oct, 28. PMID:24083949 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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