3drd

Crystal Structure of 7,8 Diaminopelargonic Acid Synthase Apoenzyme in Bacillus subtilis

spinqualitylabelsall models 3drd, resolution 2.17Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3drd is a 2 chain structure with sequence from "vibrio_subtilis"_ehrenberg_1835 "vibrio subtilis" ehrenberg 1835. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 3dod Gene: bioA ("Vibrio subtilis" Ehrenberg 1835) Activity: Adenosylmethionine--8-amino-7-oxononanoate transaminase, with EC number 2.6.1.62 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [BIOK_BACSU] Catalyzes the transfer of the alpha-amino group from L-lysine to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). B.subtilis is the only bacterium known to utilize L-lysine as an amino donor in the biosynthesis of DAPA. 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 Mycobacterium tuberculosis (Mtb) depends on biotin synthesis for survival during infection. In the absence of biotin, disruption of the biotin biosynthesis pathway results in cell death rather than growth arrest, an unusual phenotype for an Mtb auxotroph. Humans lack the enzymes for biotin production, making the proteins of this essential Mtb pathway promising drug targets. To this end, we have determined the crystal structures of the second and third enzymes of the Mtb biotin biosynthetic pathway, 7,8-diaminopelargonic acid synthase (DAPAS) and dethiobiotin synthetase (DTBS), at respective resolutions of 2.2 and 1.85 A. Superimposition of the DAPAS structures bound either to the SAM analogue sinefungin or to 7-keto-8-aminopelargonic acid (KAPA) allowed us to map the putative binding site for the substrates and to propose a mechanism by which the enzyme accommodates their disparate structures. Comparison of the DTBS structures bound to the substrate 7,8-diaminopelargonic acid (DAPA) or to ADP and the product dethiobiotin (DTB) permitted derivation of an enzyme mechanism. There are significant differences between the Mtb enzymes and those of other organisms; the Bacillus subtilis DAPAS, presented here at a high resolution of 2.2 A, has active site variations and the Escherichia coli and Helicobacter pylori DTBS have alterations in their overall folds. We have begun to exploit the unique characteristics of the Mtb structures to design specific inhibitors against the biotin biosynthesis pathway in Mtb. Structural characterization of the Mycobacterium tuberculosis biotin biosynthesis enzymes 7,8-diaminopelargonic acid synthase and dethiobiotin synthetase .,Dey S, Lane JM, Lee RE, Rubin EJ, Sacchettini JC Biochemistry. 2010 Aug 10;49(31):6746-60. PMID:20565114 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 7%2C8-diaminopelargonic acid synthase 3D structures

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