spacer
spacer

PDBsum entry 1ivh
Go to PDB code: 
protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1ivh

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chain
387 a.a. *
Ligands
FAD ×4
COS ×4
Waters ×215
* Residue conservation analysis
PDB id:
1ivh
Name: Oxidoreductase
Title: Structure of human isovaleryl-coa dehydrogenase at 2.6 angstroms resolution: structural basis for substrate specificity
Structure: Isovaleryl-coa dehydrogenase. Chain: a, b, c, d. Engineered: yes. Other_details: each subunit contains one non-covalently bound fad molecule and one non-covalently bound coa per sulfide molecule
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: liver. Organelle: mitochondria. Gene: ivd. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: the cdna was altered to accommodate escherichia coli
Biol. unit: Homo-Tetramer (from PDB file)
Resolution:
2.60Å     R-factor:   0.207     R-free:   0.288
Authors: K.A.Tiffany,D.L.Roberts,M.Wang,R.Paschke,A.-W.A.Mohsen,J.Vockley, J.J.P.Kim
Key ref:
K.A.Tiffany et al. (1997). Structure of human isovaleryl-CoA dehydrogenase at 2.6 A resolution: structural basis for substrate specificity,. Biochemistry, 36, 8455-8464. PubMed id: 9214289 DOI: 10.1021/bi970422u
Date:
15-May-97     Release date:   20-May-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P26440  (IVD_HUMAN) -  Isovaleryl-CoA dehydrogenase, mitochondrial from Homo sapiens
Seq:
Struc: 		426 a.a.
387 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.1.3.8.1  - short-chain acyl-CoA dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: a short-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H+ = a short-chain (2E)-enoyl-CoA + reduced [electron- transfer flavoprotein]
Butanoyl-CoA
Bound ligand (Het Group name = COS)
matches with 88.89% similarity 		+ electron-transfer flavoprotein
 = 2-butenoyl-CoA
 + reduced electron-transfer flavoprotein
      Cofactor: FAD
FAD
Bound ligand (Het Group name = FAD) corresponds exactly
   Enzyme class 2: E.C.1.3.8.4  - isovaleryl-CoA dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 3-methylbutanoyl-CoA + oxidized [electron-transfer flavoprotein] + H+ = 3-methylbut-2-enoyl-CoA + reduced [electron-transfer flavoprotein]
3-methylbutanoyl-CoA
Bound ligand (Het Group name = COS)
matches with 87.27% similarity 		+ oxidized [electron-transfer flavoprotein]
 + H(+)
 = 3-methylbut-2-enoyl-CoA
 + reduced [electron-transfer flavoprotein]
      Cofactor: FAD
FAD
Bound ligand (Het Group name = FAD) corresponds exactly
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1021/bi970422u Biochemistry 36:8455-8464 (1997)
PubMed id: 9214289  
 
 
Structure of human isovaleryl-CoA dehydrogenase at 2.6 A resolution: structural basis for substrate specificity,.
K.A.Tiffany, D.L.Roberts, M.Wang, R.Paschke, A.W.Mohsen, J.Vockley, J.J.Kim.
 
  ABSTRACT  
 
Isovaleryl-CoA dehydrogenase (IVD) belongs to an important flavoprotein family of acyl-CoA dehydrogenases that catalyze the alpha,beta-dehydrogenation of their various thioester substrates. Although enzymes from this family share similar sequences, catalytic mechanisms, and structural properties, the position of the catalytic base in the primary sequence is not conserved. E376 has been confirmed to be the catalytic base in medium-chain (MCAD) and short-chain acyl-CoA dehydrogenases and is conserved in all members of the acyl-CoA dehydrogenase family except for IVD and long-chain acyl-CoA dehydrogenase. To understand this dichotomy and to gain a better understanding of the factors important in determining substrate specificity in this enzyme family, the three-dimensional structure of human IVD has been determined. Human IVD expressed in Escherichia coli crystallizes in the orthorhombic space group P212121 with unit cell parameters a = 94.0 A, b = 97.7 A, and c = 181.7 A. The structure of IVD was solved at 2.6 A resolution by the molecular replacement method and was refined to an R-factor of 20.7% with an Rfree of 28.8%. The overall polypeptide fold of IVD is similar to that of other members of this family for which structural data are available. The tightly bound ligand found in the active site of the structure of IVD is consistent with that of CoA persulfide. The identity of the catalytic base was confirmed to be E254, in agreement with previous molecular modeling and mutagenesis studies. The location of the catalytic residue together with a glycine at position 374, which is a tyrosine in all other members of the acyl-CoA dehydrogenase family, is important for conferring branched-chain substrate specificity to IVD.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21040472 K.Urano, T.Daimon, Y.Banno, K.Mita, T.Terada, K.Shimizu, S.Katsuma, and T.Shimada (2010).
Molecular defect of isovaleryl-CoA dehydrogenase in the skunk mutant of silkworm, Bombyx mori.
  FEBS J, 277, 4452-4463.  
19470521 Y.Nishina, K.Sato, H.Tamaoki, C.Setoyama, R.Miura, and K.Shiga (2009).
FT-IR spectroscopic studies on the molecular mechanism for substrate specificity/activation of medium-chain Acyl-CoA dehydrogenase.
  J Biochem, 146, 351-357.  
19625492 Y.Q.Shen, B.F.Lang, and G.Burger (2009).
Diversity and dispersal of a ubiquitous protein family: acyl-CoA dehydrogenases.
  Nucleic Acids Res, 37, 5619-5631.  
19639238 Z.Swigonová, A.W.Mohsen, and J.Vockley (2009).
Acyl-CoA dehydrogenases: Dynamic history of protein family evolution.
  J Mol Evol, 69, 176-193.  
18227065 R.P.McAndrew, Y.Wang, A.W.Mohsen, M.He, J.Vockley, and J.J.Kim (2008).
Structural basis for substrate fatty acyl chain specificity: crystal structure of human very-long-chain acyl-CoA dehydrogenase.
  J Biol Chem, 283, 9435-9443.
PDB code: 3b96
18829440 T.Bowles, A.H.Metz, J.O'Quin, Z.Wawrzak, and B.F.Eichman (2008).
Structure and DNA binding of alkylation response protein AidB.
  Proc Natl Acad Sci U S A, 105, 15299-15304.
PDB code: 3djl
17374501 E.S.Goetzman, Y.Wang, M.He, A.W.Mohsen, B.K.Ninness, and J.Vockley (2007).
Expression and characterization of mutations in human very long-chain acyl-CoA dehydrogenase using a prokaryotic system.
  Mol Genet Metab, 91, 138-147.  
16887802 J.Mackenzie, L.Pedersen, S.Arent, and A.Henriksen (2006).
Controlling electron transfer in Acyl-CoA oxidases and dehydrogenases: a structural view.
  J Biol Chem, 281, 31012-31020.
PDB codes: 2ix5 2ix6
15574432 E.S.Goetzman, A.W.Mohsen, K.Prasad, and J.Vockley (2005).
Convergent evolution of a 2-methylbutyryl-CoA dehydrogenase from isovaleryl-CoA dehydrogenase in Solanum tuberosum.
  J Biol Chem, 280, 4873-4879.  
16310728 N.Nomura, M.Takada, H.Okada, Y.Shinohara, T.Nakajima-Kambe, T.Nakahara, and H.Uchiyama (2005).
Identification and functional analysis of genes required for desulfurization of alkyl dibenzothiophenes of Mycobacterium sp. G3.
  J Biosci Bioeng, 100, 398-402.  
16020546 R.Ensenauer, M.He, J.M.Willard, E.S.Goetzman, T.J.Corydon, B.B.Vandahl, A.W.Mohsen, G.Isaya, and J.Vockley (2005).
Human acyl-CoA dehydrogenase-9 plays a novel role in the mitochondrial beta-oxidation of unsaturated fatty acids.
  J Biol Chem, 280, 32309-32316.  
15272176 A.Nagpal, M.P.Valley, P.F.Fitzpatrick, and A.M.Orville (2004).
Crystallization and preliminary analysis of active nitroalkane oxidase in three crystal forms.
  Acta Crystallogr D Biol Crystallogr, 60, 1456-1460.  
15159392 H.S.Toogood, A.van Thiel, J.Basran, M.J.Sutcliffe, N.S.Scrutton, and D.Leys (2004).
Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex.
  J Biol Chem, 279, 32904-32912.
PDB code: 1t9g
14728675 J.J.Kim, and R.Miura (2004).
Acyl-CoA dehydrogenases and acyl-CoA oxidases. Structural basis for mechanistic similarities and differences.
  Eur J Biochem, 271, 483-493.  
14752098 K.P.Battaile, T.V.Nguyen, J.Vockley, and J.J.Kim (2004).
Structures of isobutyryl-CoA dehydrogenase and enzyme-product complex: comparison with isovaleryl- and short-chain acyl-CoA dehydrogenases.
  J Biol Chem, 279, 16526-16534.
PDB code: 1rx0
15159576 L.Pedersen, and A.Henriksen (2004).
Expression, purification and crystallization of two peroxisomal acyl-CoA oxidases from Arabidopsis thaliana.
  Acta Crystallogr D Biol Crystallogr, 60, 1125-1128.  
12716879 K.S.Rao, M.Albro, J.Vockley, and F.E.Frerman (2003).
Mechanism-based inactivation of human glutaryl-CoA dehydrogenase by 2-pentynoyl-CoA: rationale for enhanced reactivity.
  J Biol Chem, 278, 26342-26350.  
12936980 M.G.Thomas, Y.A.Chan, and S.G.Ozanick (2003).
Deciphering tuberactinomycin biosynthesis: isolation, sequencing, and annotation of the viomycin biosynthetic gene cluster.
  Antimicrob Agents Chemother, 47, 2823-2830.  
12855692 M.He, T.P.Burghardt, and J.Vockley (2003).
A novel approach to the characterization of substrate specificity in short/branched chain Acyl-CoA dehydrogenase.
  J Biol Chem, 278, 37974-37986.  
11812788 K.P.Battaile, J.Molin-Case, R.Paschke, M.Wang, D.Bennett, J.Vockley, and J.J.Kim (2002).
Crystal structure of rat short chain acyl-CoA dehydrogenase complexed with acetoacetyl-CoA: comparison with other acyl-CoA dehydrogenases.
  J Biol Chem, 277, 12200-12207.
PDB code: 1jqi
12220177 T.V.Nguyen, C.Riggs, D.Babovic-Vuksanovic, Y.S.Kim, J.F.Carpenter, T.P.Burghardt, N.Gregersen, and J.Vockley (2002).
Purification and characterization of two polymorphic variants of short chain acyl-CoA dehydrogenase reveal reduction of catalytic activity and stability of the Gly185Ser enzyme.
  Biochemistry, 41, 11126-11133.  
11514662 O.Dym, and D.Eisenberg (2001).
Sequence-structure analysis of FAD-containing proteins.
  Protein Sci, 10, 1712-1728.  
11231285 S.E.Faivre-Nitschke, I.Couée, M.Vermel, J.M.Grienenberger, and J.M.Gualberto (2001).
Purification, characterization and cloning of isovaleryl-CoA dehydrogenase from higher plant mitochondria.
  Eur J Biochem, 268, 1332-1339.  
10960496 C.Busquets, B.Merinero, E.Christensen, J.L.Gelpí, J.Campistol, M.Pineda, E.Fernández-Alvarez, J.M.Prats, A.Sans, R.Arteaga, M.Martí, J.Campos, M.Martínez-Pardo, A.Martínez-Bermejo, M.L.Ruiz-Falcó, J.Vaquerizo, M.Orozco, M.Ugarte, M.J.Coll, and A.Ribes (2000).
Glutaryl-CoA dehydrogenase deficiency in Spain: evidence of two groups of patients, genetically, and biochemically distinct.
  Pediatr Res, 48, 315-322.  
10713113 S.L.Volchenboum, and J.Vockley (2000).
Mitochondrial import and processing of wild type and type III mutant isovaleryl-CoA dehydrogenase.
  J Biol Chem, 275, 7958-7963.  
10985795 T.M.Dwyer, K.S.Rao, S.I.Goodman, and F.E.Frerman (2000).
Proton abstraction reaction, steady-state kinetics, and oxidation-reduction potential of human glutaryl-CoA dehydrogenase.
  Biochemistry, 39, 11488-11499.  
9665741 A.W.Mohsen, B.D.Anderson, S.L.Volchenboum, K.P.Battaile, K.Tiffany, D.Roberts, J.J.Kim, and J.Vockley (1998).
Characterization of molecular defects in isovaleryl-CoA dehydrogenase in patients with isovaleric acidemia.
  Biochemistry, 37, 10325-10335.  
9484241 K.L.Peterson, D.S.Galitz, and D.K.Srivastava (1998).
Influence of excision of a methylene group from Glu-376 (Glu376-->Asp mutation) in the medium chain acyl-CoA dehydrogenase-catalyzed reaction.
  Biochemistry, 37, 1697-1705.  
9817851 Y.Modis, and R.Wierenga (1998).
Two crystal structures of N-acetyltransferases reveal a new fold for CoA-dependent enzymes.
  Structure, 6, 1345-1350.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

spacer
spacer