3ano | pdb_00003ano

Crystal Structure of a Novel Diadenosine 5',5-P1,P4-Tetraphosphate Phosphorylase from Mycobacterium tuberculosis H37Rv

spinqualitylabelsall models 3ano, resolution 1.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ano is a 2 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.894Å Ligands: PG4, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AP4A_MYCTU Catabolizes diadenosine 5',5-P1,P4-tetraphosphate (Ap4A) into ADP and ATP. It does not catalyze the reverse phosphorolysis reaction. The optimum substrates are dinucleoside polyphosphates containing four or five phosphate residues. Publication Abstract from PubMed Rv2613c is a diadenosine 5',5-P(1),P(4)-tetraphosphate (Ap(4)A) phosphorylase from Mycobacterium tuberculosis H37Rv. Sequence analysis suggests that Rv2613c belongs to the histidine triad (HIT) motif superfamily, which includes HIT family diadenosine polyphosphate (Ap(n)A) hydrolases and Ap(4)A phosphorylases. However, the amino acid sequence of Rv2613c is more similar to that of HIT family Ap(n)A hydrolases than to that of typical Ap(4)A phosphorylases. Here, we report the crystal structure of Rv2613c, which is the first structure of a protein with Ap(n)A phosphorylase activity, and characterized the structural basis of its catalytic activity. Our results showed that the structure of Rv2613c is similar to those of other HIT superfamily proteins. However, Asn139, Gly146, and Ser147 in the active site of Rv2613c replace the corresponding Gln, Gln, and Thr residues that are normally found in HIT family Ap(n)A hydrolases. Furthermore, analyses of Rv2613c mutants revealed that Asn139, Gly146, and Ser147 are important active-site residues and that Asn139 has a critical role in catalysis. The position of Gly146 might influence the phosphorylase activity. In addition, the tetrameric structure of Rv2613c and the presence of Trp160 might be essential for the formation of the Ap(4)A binding site. These structural insights into Rv2613c may facilitate the development of novel structure-based inhibitors for treating tuberculosis. Structural insights into the novel diadenosine 5',5-P(1),P(4)-tetraphosphate phosphorylase from Mycobacterium tuberculosis H37Rv.,Mori S, Shibayama K, Wachino J, Arakawa Y J Mol Biol. 2011 Jul 1;410(1):93-104. doi: 10.1016/j.jmb.2011.04.059. Epub 2011, May 4. PMID:21565198 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA