Crystal structure of Rv0805 D66A mutantCrystal structure of Rv0805 D66A mutant
Structural highlights
2hyp is a 1 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.
CNPD3_MYCTU Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP (PubMed:16313172, PubMed:18757371). Can use 2',3'-cAMP, 2',3'-cGMP, 3',5'-cAMP, 3',5'-cGMP and 3',5'-cUMP (PubMed:16313172, PubMed:18757371, PubMed:19801656). Hydrolysis of 2',3'-cAMP produces a mixture of 3'-AMP (major product) and 2'-AMP (minor product) (PubMed:18757371). In vitro, is 150-fold more active in hydrolyzing 2',3'-cAMP than 3',5'-cAMP (PubMed:18757371). Can also hydrolyze the model substrates p-nitrophenyl phosphate (pNPP), bis-(p-nitrophenyl phosphate) (bis(pNPP)) and p-nitrophenyl phenylphosphonate (pNPPP) (PubMed:16313172, PubMed:18757371, PubMed:19801656). Plays an important regulatory role in modulating the intracellular concentration of cAMP, thereby influencing cAMP-dependent processes (PubMed:16313172). May play a role in pathogenicity, not only by hydrolyzing cAMP, but also by altering properties of the cell wall (PubMed:19801656).[1][2][3] Overexpression elicits a transcriptional response that is independent of the phosphodiesterase activity. It does not alter the levels of cAMP-CRP regulated genes, even though cAMP levels are reduced in cells.[4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
↑Shenoy AR, Sreenath N, Podobnik M, Kovacevic M, Visweswariah SS. The Rv0805 gene from Mycobacterium tuberculosis encodes a 3',5'-cyclic nucleotide phosphodiesterase: biochemical and mutational analysis. Biochemistry. 2005 Dec 6;44(48):15695-704. PMID:16313172 doi:10.1021/bi0512391
↑Keppetipola N, Shuman S. A phosphate-binding histidine of binuclear metallophosphodiesterase enzymes is a determinant of 2',3'-cyclic nucleotide phosphodiesterase activity. J Biol Chem. 2008 Nov 7;283(45):30942-9. PMID:18757371 doi:10.1074/jbc.M805064200
↑Podobnik M, Tyagi R, Matange N, Dermol U, Gupta AK, Mattoo R, Seshadri K, Visweswariah SS. A mycobacterial cyclic AMP phosphodiesterase that moonlights as a modifier of cell wall permeability. J Biol Chem. 2009 Nov 20;284(47):32846-57. Epub 2009 Sep 29. PMID:19801656 doi:10.1074/jbc.M109.049635
↑Matange N, Hunt DM, Buxton RS, Visweswariah SS. Overexpression of the Rv0805 phosphodiesterase elicits a cAMP-independent transcriptional response. Tuberculosis (Edinb). 2013 Sep;93(5):492-500. PMID:23835087 doi:10.1016/j.tube.2013.05.004
