4x58 | pdb_00004x58

Anthranilate phosphoribosyl transferase variant N138A from Mycobacterium tuberculosis in complex with PRPP and Mg

spinqualitylabelsall models 4x58, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4x58 is a 2 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, IMD, MG, MLT, PRP Related: 4x59, 4x5a, 4x5b, 4x5c, 4x5d, 4x5e Gene: trpD ("Bacillus tuberculosis" (Zopf 1883) Klein 1884) Activity: Anthranilate phosphoribosyltransferase, with EC number 2.4.2.18 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TRPD_MYCTA] Catalyzes the transfer of the phosphoribosyl group of 5-phosphorylribose-1-pyrophosphate (PRPP) to anthranilate to yield N-(5'-phosphoribosyl)-anthranilate (PRA). Publication Abstract from PubMed Anthranilate phosphoribosyltransferase (AnPRT) is essential for the biosynthesis of tryptophan in Mycobacterium tuberculosis (Mtb). This enzyme catalyzes the second committed step in tryptophan biosynthesis, the Mg(2+)-dependent reaction between 5'-phosphoribosyl-1'-pyrophosphate (PRPP) and anthranilate. The roles of residues predicted to be involved in anthranilate binding have been tested by the analysis of six Mtb-AnPRT variant proteins. Kinetic analysis showed that five of six variants were active and identified the conserved residue R193 as being crucial for both anthranilate binding and catalytic function. Crystal structures of these Mtb-AnPRT variants reveal the ability of anthranilate to bind in three sites along an extended anthranilate tunnel and expose the role of the mobile beta2-alpha6 loop in facilitating the enzyme's sequential reaction mechanism. The beta2-alpha6 loop moves sequentially between a "folded" conformation, partially occluding the anthranilate tunnel, via an "open" position to a "closed" conformation, which supports PRPP binding and allows anthranilate access via the tunnel to the active site. The return of the beta2-alpha6 loop to the "folded" conformation completes the catalytic cycle, concordantly allowing the active site to eject the product PRA and rebind anthranilate at the opening of the anthranilate tunnel for subsequent reactions. Multiple anthranilate molecules blocking the anthranilate tunnel prevent the beta2-alpha6 loop from undergoing the conformational changes required for catalysis, thus accounting for the unusual substrate inhibition of this enzyme. Structures of Mycobacterium tuberculosis Anthranilate Phosphoribosyltransferase Variants Reveal the Conformational Changes That Facilitate Delivery of the Substrate to the Active Site.,Cookson TV, Evans GL, Castell A, Baker EN, Lott JS, Parker EJ Biochemistry. 2015 Oct 6;54(39):6082-92. doi: 10.1021/acs.biochem.5b00612. PMID:26356348 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoribosyltransferase

Proteopedia Page Contributors and Editors (what is this?)

OCA