3mgz

Crystal structure of DHBPS domain of bi-functional DHBPS/GTP cyclohydrolase II from Mycobacterium tuberculosis at pH 4.0

spinqualitylabelsall models 3mgz, resolution 2.07Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3mgz is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Ra. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.07Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RIBBA_MYCTA Catalyzes the conversion of D-ribulose 5-phosphate to formate and 3,4-dihydroxy-2-butanone 4-phosphate (By similarity). Catalyzes the conversion of GTP to 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (DARP), formate and pyrophosphate (By similarity). Publication Abstract from PubMed 3,4-dihydroxy 2-butanone 4-phosphate synthase (DHBPS) and GTP cyclohydrolase-II (GTPCH-II) are the two initial enzymes involved in riboflavin biosynthesis pathway, which has been shown to be essential for the pathogens. In Mycobacterium tuberculosis (Mtb), the ribA2 gene (Rv1415) encodes for the bi-functional enzyme with DHBPS and GTPCH-II domains at N- and C-termini, respectively. We have determined three crystal structures of Mtb-DHBPS domain in complex with phosphate and glycerol at pH 6.0, with sulphate at pH 4.0 and with zinc and sulphate at pH 4.0 at 1.8, 2.06 and 2.06A resolution, respectively. The hydrodynamic volume and enzyme activity studies revealed that the Mtb-DHBPS domain forms a functional homo-dimer between the pH 6.0 and 9.0, however, at pH 5.0 and below, it forms a stable inactive monomer in solution. Furthermore, the functional activity of Mtb-DHBPS and its dimeric state could be restored by increasing the pH between 6.0 and 9.0. The comparison of crystal structures determined at different pH revealed that the overall three-dimensional structure of Mtb-DHBPS monomer remains the same. However, the length of the alpha6-helix at pH 6.0 has increased from 15 to 22A in pH 4.0 by increasing the number of amino acids contributing to the alpha6-helix from 11 to 15, achieving a higher structural stability at pH 4.0. Taken together our experiments strongly suggest that the Mtb-DHBPS domain can transit between inactive monomer to active dimer depending upon its pH values, both in solution as well in crystal structure. Structural basis for pH dependent monomer-dimer transition of 3,4-dihydroxy 2-butanone-4-phosphate synthase domain from Mycobacterium tuberculosis.,Singh M, Kumar P, Karthikeyan S J Struct Biol. 2011 Feb 4. PMID:21296160 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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