3mwe

Truncated Human ATP-Citrate Lyase with Tartrate Bound

spinqualitylabelsall models 3mwe, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3mwe is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, TLA Related: 3mwd Gene: ACLY (HUMAN) Activity: ATP citrate synthase, with EC number 2.3.3.8 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ACLY_HUMAN] ATP citrate-lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Has a central role in de novo lipid synthesis. In nervous tissue it may be involved in the biosynthesis of acetylcholine. 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 ATP-citrate lyase (ACLY) catalyzes the conversion of citrate and CoA into acetyl-CoA and oxaloacetate, coupled with the hydrolysis of ATP. In humans, ACLY is the cytoplasmic enzyme linking energy metabolism from carbohydrates to the production of fatty acids. In situ proteolysis of full-length human ACLY gave crystals of a truncated form, revealing the conformations of residues 2-425, 487-750, and 767-820 of the 1101-amino acid protein. Residues 2-425 form three domains homologous to the beta-subunit of succinyl-CoA synthetase (SCS), while residues 487-820 form two domains homologous to the alpha-subunit of SCS. The crystals were grown in the presence of tartrate or the substrate, citrate, and the structure revealed the citrate-binding site. A loop formed by residues 343-348 interacts via specific hydrogen bonds with the hydroxyl and carboxyl groups on the prochiral center of citrate. Arg-379 forms a salt bridge with the pro-R carboxylate of citrate. The pro-S carboxylate is free to react, providing insight into the stereospecificity of ACLY. Because this is the first structure of any member of the acyl-CoA synthetase (NDP-forming) superfamily in complex with its organic acid substrate, locating the citrate-binding site is significant for understanding the catalytic mechanism of each member, including the prototype SCS. Comparison of the CoA-binding site of SCSs with the similar structure in ACLY showed that ACLY possesses a different CoA-binding site. Comparisons of the nucleotide-binding site of SCSs with the similar structure in ACLY indicates that this is the ATP-binding site of ACLY. Identification of the citrate-binding site of human ATP-citrate lyase using X-ray crystallography.,Sun T, Hayakawa K, Bateman KS, Fraser ME J Biol Chem. 2010 Aug 27;285(35):27418-28. Epub 2010 Jun 17. PMID:20558738 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also ATP-citrate synthase

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