5mdh

CRYSTAL STRUCTURE OF TERNARY COMPLEX OF PORCINE CYTOPLASMIC MALATE DEHYDROGENASE ALPHA-KETOMALONATE AND TNAD AT 2.4 ANGSTROMS RESOLUTION

spinqualitylabelsall models 5mdh, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5mdh is a 2 chain structure with sequence from Sus scrofa. The October 2012 RCSB PDB Molecule of the Month feature on Citric Acid Cycle by David Goodsell is 10.2210/rcsb_pdb/mom_2012_10. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: MAK, NAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MDHC_PIG 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 The structural basis for the extreme discrimination achieved by malate dehydrogenases between a variety of closely related substrates encountered within the cell has been difficult to assess because of the lack of an appropriate catalytically competent structure of the enzyme. Here, we have determined the crystal structure of a ternary complex of porcine cytoplasmic malate dehydrogenase with the alternative substrate alpha-ketomalonate and the coenzyme analogue 1,4,5,6-tetrahydronicotinamide. Both subunits of the dimeric porcine heart, and from the prokaryotes Escherichia coli and Thermus flavus. However, large changes are noted around the active site, where a mobile loop now closes to bring key residues into contact with the substrate. This observation substantiates a postulated mechanism in which the enzyme achieves high levels of substrate discrimination through charge balancing in the active site. As the activated cofactor/substrate complex has a net negative charge, a positive counter-charge is provided by a conserved arginine in the active site loop. The enzyme must, however, also discriminate against smaller substrates, such as pyruvate. The structure shows in the closed (loop down) catalytically competent complex two arginine residues (91 and 97) are driven into close proximity. Without the complimentary, negative charge of the substrate side-chain of oxaloacetate or alpha-ketomalonate, charge repulsion would resist formation production of this catalytically productive conformation, hence minimising the effectiveness of pyruvate as a substrate. By this mechanism, malate dehydrogenase uses charge balancing to achieve fivefold orders of magnitude in discrimination between potential substrates. Structural basis of substrate specificity in malate dehydrogenases: crystal structure of a ternary complex of porcine cytoplasmic malate dehydrogenase, alpha-ketomalonate and tetrahydoNAD.,Chapman AD, Cortes A, Dafforn TR, Clarke AR, Brady RL J Mol Biol. 1999 Jan 15;285(2):703-12. PMID:10075524 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Malate Dehydrogenase 3D structures

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