5x8f

Ternary complex structure of a double mutant I454RA456K of o-Succinylbenzoate CoA Synthetase (MenE) from Bacillus Subtilis bound with AMP and its product analogue OSB-NCoA at 1.76 angstrom

spinqualitylabelsall models 5x8f, resolution 1.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5x8f is a 4 chain structure with sequence from Bacillus subtilis subsp. subtilis str. 168. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.763Å Ligands: AMP, CA, MG, NA, PEG, S0N Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MENE_BACSU Converts 2-succinylbenzoate (OSB) to 2-succinylbenzoyl-CoA (OSB-CoA).[HAMAP-Rule:MF_00731] Publication Abstract from PubMed o-Succinylbenzoyl-CoA (OSB-CoA) synthetase (MenE) is an essential enzyme in bacterial vitamin K biosynthesis and an important target in the development of new antibiotics. It is a member of the adenylating enzymes (ANL) family, which reconfigure their active site in two different active conformations, one for the adenylation half-reaction and the other for a thioesterification half-reaction, in a domain-alternation catalytic mechanism. Although several aspects of the adenylating mechanism in MenE have recently been uncovered, its thioesterification conformation remains elusive. Here, using a catalytically competent Bacillus subtilis mutant protein complexed with an OSB-CoA analogue, we determined MenE high-resolution structures to 1.76 and 1.90 A resolution in a thioester-forming conformation. By comparison with the adenylation conformation, we found that MenE's C-domain rotates around the Ser-384 hinge by 139.5 degrees during domain-alternation catalysis. The structures also revealed a thioesterification active site specifically conserved among MenE orthologues and a substrate-binding mode distinct from those of many other acyl/aryl-CoA synthetases. Of note, using site-directed mutagenesis, we identified several residues that specifically contribute to the thioesterification half-reaction without affecting the adenylation half-reaction. Moreover, we observed a substantial movement of the activated succinyl group in the thioesterification half-reaction. These findings provide new insights into the domain-alternation catalysis of a bacterial enzyme essential for vitamin K biosynthesis and of its adenylating homologues in the ANL enzyme family. Crystal structure of the thioesterification conformation of Bacillus subtilis o-succinylbenzoyl-CoA synthetase reveals a distinct substrate-binding mode.,Chen Y, Li TL, Lin X, Li X, Li XD, Guo Z J Biol Chem. 2017 Jul 21;292(29):12296-12310. doi: 10.1074/jbc.M117.790410. Epub , 2017 May 30. PMID:28559280 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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