1ege › Citations

Crystal structures of the wild type and the Glu376Gly/Thr255Glu mutant of human medium-chain acyl-CoA dehydrogenase: influence of the location of the catalytic base on substrate specificity.

Lee HJ, Wang M, Paschke R, Nandy A, Ghisla S, Kim JJ
Biochemistry 35 12412-20 (1996)
Related entries: 1egc, 1egd

Cited: 41 times
EuropePMC logo PMID: 8823176

Abstract

Crystal structures of the wild type human medium-chain acyl-CoA dehydrogenase (MCADH) and a double mutant in which its active center base-arrangement has been altered to that of long chain acyl-CoA dehydrogenase (LCADH), Glu376Gly/Thr255Glu, have been determined by X-ray crystallography at 2.75 and 2.4 A resolution, respectively. The catalytic base responsible for the alpha-proton abstraction from the thioester substrate is Glu376 in MCADH, while that in LCADH is Glu255 (MCADH numbering), located over 100 residues away in its primary amino acid sequence. The structures of the mutant complexed with C8-, C12, and C14-CoA have also been determined. The human enzyme structure is essentially the same as that of the pig enzyme. The structure of the mutant is unchanged upon ligand binding except for the conformations of a few side chains in the active site cavity. The substrate with chain length longer than C12 binds to the enzyme in multiple conformations at its omega-end. Glu255 has two conformations, "active" and "resting" forms, with the latter apparently stabilized by forming a hydrogen bond with Glu99. Both the direction in which Glu255 approaches the C alpha atom of the substrate and the distance between the Glu255 carboxylate and the C alpha atom are different from those of Glu376; these factors are responsible for the intrinsic differences in the kinetic properties as well as the substrate specificity. Solvent accessible space at the "midsection" of the active site cavity, where the C alpha-C beta bond of the thioester substrate and the isoalloxazine ring of the FAD are located, is larger in the mutant than in the wild type enzyme, implying greater O2 accessibility in the mutant which might account for the higher oxygen reactivity.

Reviews - 1ege mentioned but not cited (1)

  1. The role of protein complexes in human genetic disease. Bergendahl LT, Gerasimavicius L, Miles J, Macdonald L, Wells JN, Welburn JPI, Marsh JA. Protein Sci 28 1400-1411 (2019)

Articles - 1ege mentioned but not cited (5)

  1. Deamidation of human proteins. Robinson NE, Robinson AB. Proc Natl Acad Sci U S A 98 12409-12413 (2001)
  2. Sensitivity of molecular dynamics simulations to the choice of the X-ray structure used to model an enzymatic reaction. Garcia-Viloca M, Poulsen TD, Truhlar DG, Gao J. Protein Sci 13 2341-2354 (2004)
  3. Influence of Disease-Causing Mutations on Protein Structural Networks. Prabantu VM, Naveenkumar N, Srinivasan N. Front Mol Biosci 7 620554 (2020)
  4. Structural similarity and classification of protein interaction interfaces. Zhao N, Pang B, Shyu CR, Korkin D. PLoS One 6 e19554 (2011)
  5. Medium-chain acyl-CoA deficiency: outlines from newborn screening, in silico predictions, and molecular studies. Catarzi S, Caciotti A, Thusberg J, Tonin R, Malvagia S, la Marca G, Pasquini E, Cavicchi C, Ferri L, Donati MA, Baronio F, Guerrini R, Mooney SD, Morrone A. ScientificWorldJournal 2013 625824 (2013)


Reviews citing this publication (6)

  1. Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype-phenotype relationship. Gregersen N, Andresen BS, Corydon MJ, Corydon TJ, Olsen RK, Bolund L, Bross P. Hum Mutat 18 169-189 (2001)
  2. Acyl-CoA dehydrogenases and acyl-CoA oxidases. Structural basis for mechanistic similarities and differences. Kim JJ, Miura R. Eur J Biochem 271 483-493 (2004)
  3. Dynamics driving function: new insights from electron transferring flavoproteins and partner complexes. Toogood HS, Leys D, Scrutton NS. FEBS J 274 5481-5504 (2007)
  4. Nitroalkane oxidase, a carbanion-forming flavoprotein homologous to acyl-CoA dehydrogenase. Fitzpatrick PF, Orville AM, Nagpal A, Valley MP. Arch Biochem Biophys 433 157-165 (2005)
  5. Structure and function of plant acyl-CoA oxidases. Arent S, Pye VE, Henriksen A. Plant Physiol Biochem 46 292-301 (2008)
  6. Structure of D-amino acid oxidase: new insights from an old enzyme. Mattevi A, Vanoni MA, Curti B. Curr Opin Struct Biol 7 804-810 (1997)

Articles citing this publication (29)

  1. Characterization of the pyoluteorin biosynthetic gene cluster of Pseudomonas fluorescens Pf-5. Nowak-Thompson B, Chaney N, Wing JS, Gould SJ, Loper JE. J Bacteriol 181 2166-2174 (1999)
  2. MS/MS-based newborn and family screening detects asymptomatic patients with very-long-chain acyl-CoA dehydrogenase deficiency. Spiekerkoetter U, Sun B, Zytkovicz T, Wanders R, Strauss AW, Wendel U. J Pediatr 143 335-342 (2003)
  3. Acyl-CoA dehydrogenases: Dynamic history of protein family evolution. Swigonová Z, Mohsen AW, Vockley J. J Mol Evol 69 176-193 (2009)
  4. Structural basis for substrate fatty acyl chain specificity: crystal structure of human very-long-chain acyl-CoA dehydrogenase. McAndrew RP, Wang Y, Mohsen AW, He M, Vockley J, Kim JJ. J Biol Chem 283 9435-9443 (2008)
  5. Beta-oxidation of 5-hydroxydecanoate, a putative blocker of mitochondrial ATP-sensitive potassium channels. Hanley PJ, Gopalan KV, Lareau RA, Srivastava DK, von Meltzer M, Daut J. J Physiol 547 387-393 (2003)
  6. Human acyl-CoA dehydrogenase-9 plays a novel role in the mitochondrial beta-oxidation of unsaturated fatty acids. Ensenauer R, He M, Willard JM, Goetzman ES, Corydon TJ, Vandahl BB, Mohsen AW, Isaya G, Vockley J. J Biol Chem 280 32309-32316 (2005)
  7. Insights into Disease-Associated Mutations in the Human Proteome through Protein Structural Analysis. Gao M, Zhou H, Skolnick J. Structure 23 1362-1369 (2015)
  8. Crystal structure of rat short chain acyl-CoA dehydrogenase complexed with acetoacetyl-CoA: comparison with other acyl-CoA dehydrogenases. Battaile KP, Molin-Case J, Paschke R, Wang M, Bennett D, Vockley J, Kim JJ. J Biol Chem 277 12200-12207 (2002)
  9. Shrinking the FadE proteome of Mycobacterium tuberculosis: insights into cholesterol metabolism through identification of an α2β2 heterotetrameric acyl coenzyme A dehydrogenase family. Wipperman MF, Yang M, Thomas ST, Sampson NS. J Bacteriol 195 4331-4341 (2013)
  10. Inversion of stereospecificity of vanillyl-alcohol oxidase. van Den Heuvel RH, Fraaije MW, Ferrer M, Mattevi A, van Berkel WJ. Proc Natl Acad Sci U S A 97 9455-9460 (2000)
  11. Stabilization of non-productive conformations underpins rapid electron transfer to electron-transferring flavoprotein. Toogood HS, van Thiel A, Scrutton NS, Leys D. J Biol Chem 280 30361-30366 (2005)
  12. Crystal structure of an Acyl-ACP dehydrogenase from the FK520 polyketide biosynthetic pathway: insights into extender unit biosynthesis. Watanabe K, Khosla C, Stroud RM, Tsai SC. J Mol Biol 334 435-444 (2003)
  13. Acyl-CoA oxidase 1 from Arabidopsis thaliana. Structure of a key enzyme in plant lipid metabolism. Pedersen L, Henriksen A. J Mol Biol 345 487-500 (2005)
  14. Full-length, Oligomeric Structure of Wzz Determined by Cryoelectron Microscopy Reveals Insights into Membrane-Bound States. Collins RF, Kargas V, Clarke BR, Siebert CA, Clare DK, Bond PJ, Whitfield C, Ford RC. Structure 25 806-815.e3 (2017)
  15. A novel approach to the characterization of substrate specificity in short/branched chain Acyl-CoA dehydrogenase. He M, Burghardt TP, Vockley J. J Biol Chem 278 37974-37986 (2003)
  16. Identification of the catalytic residue of human short/branched chain acyl-CoA dehydrogenase by in vitro mutagenesis. Binzak B, Willard J, Vockley J. Biochim Biophys Acta 1382 137-142 (1998)
  17. Characterization of human and pig kidney long-chain-acyl-CoA dehydrogenases and their role in beta-oxidation. Eder M, Kräutle F, Dong Y, Vock P, Kieweg V, Kim JJ, Strauss AW, Ghisla S. Eur J Biochem 245 600-607 (1997)
  18. Potential of mean force calculation for the proton and hydride transfer reactions catalyzed by medium-chain acyl-CoA dehydrogenase: effect of mutations on enzyme catalysis. Bhattacharyya S, Ma S, Stankovich MT, Truhlar DG, Gao J. Biochemistry 44 16549-16562 (2005)
  19. Crystallization and preliminary analysis of active nitroalkane oxidase in three crystal forms. Nagpal A, Valley MP, Fitzpatrick PF, Orville AM. Acta Crystallogr D Biol Crystallogr 60 1456-1460 (2004)
  20. Influence of Glu-376 --> Gln mutation on enthalpy and heat capacity changes for the binding of slightly altered ligands to medium chain acyl-CoA dehydrogenase. Peterson KM, Gopalan KV, Nandy A, Srivastava DK. Protein Sci 10 1822-1834 (2001)
  21. Structure of the prolyl-acyl carrier protein oxidase involved in the biosynthesis of the cyanotoxin anatoxin-a. Moncoq K, Regad L, Mann S, Méjean A, Ploux O. Acta Crystallogr D Biol Crystallogr 69 2340-2352 (2013)
  22. Functional studies of 18 heterologously expressed medium-chain acyl-CoA dehydrogenase (MCAD) variants. Koster KL, Sturm M, Herebian D, Smits SH, Spiekerkoetter U. J Inherit Metab Dis 37 917-928 (2014)
  23. A covalent adduct of MbtN, an acyl-ACP dehydrogenase from Mycobacterium tuberculosis, reveals an unusual acyl-binding pocket. Chai AF, Bulloch EM, Evans GL, Lott JS, Baker EN, Johnston JM. Acta Crystallogr D Biol Crystallogr 71 862-872 (2015)
  24. Redesigning the active-site of an acyl-CoA dehydrogenase: new evidence supporting a one-base mechanism. Dakoji S, Shin I, Battaile KP, Vockley J, Liu HW. Bioorg Med Chem 5 2157-2164 (1997)
  25. Fluoromorphic substrates for fatty acid metabolism: highly sensitive probes for mammalian medium-chain acyl-CoA dehydrogenase. Froemming MK, Sames D. Angew Chem Int Ed Engl 45 637-642 (2006)
  26. Functional analysis of acyl-CoA dehydrogenase catalytic residue mutants using surface plasmon resonance and circular dichroism. Goetzman ES, He M, Nguyen TV, Vockley J. Mol Genet Metab 87 233-242 (2006)
  27. Insights into Medium-chain Acyl-CoA Dehydrogenase Structure by Molecular Dynamics Simulations. Bonito CA, Leandro P, Ventura FV, Guedes RC. Chem Biol Drug Des 88 281-292 (2016)
  28. FT-IR spectroscopic studies on the molecular mechanism for substrate specificity/activation of medium-chain acyl-CoA dehydrogenase. Nishina Y, Sato K, Tamaoki H, Setoyama C, Miura R, Shiga K. J Biochem 146 351-357 (2009)
  29. High-Resolution Structural Proteomics of Mitochondria Using the 'Build and Retrieve' Methodology. Zhang Z, Tringides ML, Morgan CE, Miyagi M, Mears JA, Hoppel CL, Yu EW. Mol Cell Proteomics 22 100666 (2023)


Quick links