PDBsum entry 2hdh

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Oxidoreductase PDB id
Protein chain
293 a.a. *
NAD ×2
Waters ×253
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Biochemical characterization and structure determination of heart short chain l-3-hydroxyacyl coa dehydrogenase provide into catalytic mechanism
Structure: L-3-hydroxyacyl coa dehydrogenase. Chain: a, b. Synonym: schad. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: heart. Organelle: mitochondrial. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: expressed as selenomethionine-substituted pr protein was expressed with a c-terminal hexameric histidine
Biol. unit: Dimer (from PQS)
2.20Å     R-factor:   0.198     R-free:   0.251
Authors: J.J.Barycki,J.M.Bratt,L.J.Banaszak
Key ref:
J.J.Barycki et al. (1999). Biochemical characterization and crystal structure determination of human heart short chain L-3-hydroxyacyl-CoA dehydrogenase provide insights into catalytic mechanism. Biochemistry, 38, 5786-5798. PubMed id: 10231530 DOI: 10.1021/bi9829027
04-Dec-98     Release date:   12-May-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q16836  (HCDH_HUMAN) -  Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial
314 a.a.
293 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - 3-hydroxyacyl-CoA dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (S)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH
Bound ligand (Het Group name = NAD)
corresponds exactly
= 3-oxoacyl-CoA
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   6 terms 
  Biological process     small molecule metabolic process   11 terms 
  Biochemical function     oxidoreductase activity     5 terms  


DOI no: 10.1021/bi9829027 Biochemistry 38:5786-5798 (1999)
PubMed id: 10231530  
Biochemical characterization and crystal structure determination of human heart short chain L-3-hydroxyacyl-CoA dehydrogenase provide insights into catalytic mechanism.
J.J.Barycki, L.K.O'Brien, J.M.Bratt, R.Zhang, R.Sanishvili, A.W.Strauss, L.J.Banaszak.
Human heart short chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) catalyzes the oxidation of the hydroxyl group of L-3-hydroxyacyl-CoA to a keto group, concomitant with the reduction of NAD+ to NADH, as part of the beta-oxidation pathway. The homodimeric enzyme has been overexpressed in Escherichia coli, purified to homogeneity, and studied using biochemical and crystallographic techniques. The dissociation constants of NAD+ and NADH have been determined over a broad pH range and indicate that SCHAD binds reduced cofactor preferentially. Examination of apparent catalytic constants reveals that SCHAD displays optimal enzymatic activity near neutral pH, with catalytic efficiency diminishing rapidly toward pH extremes. The crystal structure of SCHAD complexed with NAD+ has been solved using multiwavelength anomalous diffraction techniques and a selenomethionine-substituted analogue of the enzyme. The subunit structure is comprised of two domains. The first domain is similar to other alpha/beta dinucleotide folds but includes an unusual helix-turn-helix motif which extends from the central beta-sheet. The second, or C-terminal, domain is primarily alpha-helical and mediates subunit dimerization and, presumably, L-3-hydroxyacyl-CoA binding. Molecular modeling studies in which L-3-hydroxybutyryl-CoA was docked into the enzyme-NAD+ complex suggest that His 158 serves as a general base, abstracting a proton from the 3-OH group of the substrate. Furthermore, the ability of His 158 to perform such a function may be enhanced by an electrostatic interaction with Glu 170, consistent with previous biochemical observations. These studies provide further understanding of the molecular basis of several inherited metabolic disease states correlated with L-3-hydroxyacyl-CoA dehydrogenase deficiencies.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20054534 J.Parkot, H.Gröger, and W.Hummel (2010).
Purification, cloning, and overexpression of an alcohol dehydrogenase from Nocardia globerula reducing aliphatic ketones and bulky ketoesters.
  Appl Microbiol Biotechnol, 86, 1813-1820.  
20378648 R.C.Taylor, A.K.Brown, A.Singh, A.Bhatt, and G.S.Besra (2010).
Characterization of a beta-hydroxybutyryl-CoA dehydrogenase from Mycobacterium tuberculosis.
  Microbiology, 156, 1975-1982.  
19218190 N.Yokochi, Y.Yoshikane, S.Matsumoto, M.Fujisawa, K.Ohnishi, and T.Yagi (2009).
Gene identification and characterization of 5-formyl-3-hydroxy-2-methylpyridine 4-carboxylic acid 5-dehydrogenase, an NAD+-dependent dismutase.
  J Biochem, 145, 493-503.  
18652860 R.S.Rector, R.M.Payne, and J.A.Ibdah (2008).
Mitochondrial trifunctional protein defects: clinical implications and therapeutic approaches.
  Adv Drug Deliv Rev, 60, 1488-1496.  
  18323616 Y.Asada, C.Kuroishi, Y.Ukita, R.Sumii, S.Endo, T.Matsunaga, A.Hara, and N.Kunishima (2008).
Crystallization and preliminary X-ray crystallographic analysis of rabbit L-gulonate 3-dehydrogenase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 228-230.  
17229734 A.Ciulli, D.Y.Chirgadze, A.G.Smith, T.L.Blundell, and C.Abell (2007).
Crystal structure of Escherichia coli ketopantoate reductase in a ternary complex with NADP+ and pantoate bound: substrate recognition, conformational change, and cooperativity.
  J Biol Chem, 282, 8487-8497.
PDB code: 2ofp
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.  
16513644 W.Sun, S.Singh, R.Zhang, J.L.Turnbull, and D.Christendat (2006).
Crystal structure of prephenate dehydrogenase from Aquifex aeolicus. Insights into the catalytic mechanism.
  J Biol Chem, 281, 12919-12928.
PDB code: 2g5c
16169737 A.Li, T.Itoh, T.Taguchi, T.Xiang, Y.Ebizuka, and K.Ichinose (2005).
Functional studies on a ketoreductase gene from Streptomyces sp. AM-7161 to control the stereochemistry in medermycin biosynthesis.
  Bioorg Med Chem, 13, 6856-6863.  
16233902 B.Nocek, C.Chang, H.Li, L.Lezondra, D.Holzle, F.Collart, and A.Joachimiak (2005).
Crystal structures of delta1-pyrroline-5-carboxylate reductase from human pathogens Neisseria meningitides and Streptococcus pyogenes.
  J Mol Biol, 354, 91.
PDB codes: 1yqg 2ag8 2ahr 2amf
16176262 S.Y.Yang, X.Y.He, and H.Schulz (2005).
3-Hydroxyacyl-CoA dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease.
  FEBS J, 272, 4874-4883.  
  15314688 K.A.Lantz, M.Z.Vatamaniuk, J.E.Brestelli, J.R.Friedman, F.M.Matschinsky, and K.H.Kaestner (2004).
Foxa2 regulates multiple pathways of insulin secretion.
  J Clin Invest, 114, 512-520.  
15229654 M.Ishikawa, D.Tsuchiya, T.Oyama, Y.Tsunaka, and K.Morikawa (2004).
Structural basis for channelling mechanism of a fatty acid beta-oxidation multienzyme complex.
  EMBO J, 23, 2745-2754.
PDB codes: 1wdk 1wdl 1wdm
15016352 S.W.Aufhammer, E.Warkentin, H.Berk, S.Shima, R.K.Thauer, and U.Ermler (2004).
Coenzyme binding in F420-dependent secondary alcohol dehydrogenase, a member of the bacterial luciferase family.
  Structure, 12, 361-370.
PDB code: 1rhc
14630990 U.Spiekerkoetter, Z.Khuchua, Z.Yue, M.J.Bennett, and A.W.Strauss (2004).
General mitochondrial trifunctional protein (TFP) deficiency as a result of either alpha- or beta-subunit mutations exhibits similar phenotypes because mutations in either subunit alter TFP complex expression and subunit turnover.
  Pediatr Res, 55, 190-196.  
11914498 J.P.Taskinen, T.R.Kiema, K.T.Koivuranta, R.K.Wierenga, and J.K.Hiltunen (2002).
Crystallization and characterization of the dehydrogenase domain from rat peroxisomal multifunctional enzyme type 1.
  Acta Crystallogr D Biol Crystallogr, 58, 690-693.  
12394635 J.Vockley, R.H.Singh, and D.A.Whiteman (2002).
Diagnosis and management of defects of mitochondrial beta-oxidation.
  Curr Opin Clin Nutr Metab Care, 5, 601-609.  
11418771 D.G.Levitt (2001).
A new software routine that automates the fitting of protein X-ray crystallographic electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 57, 1013-1019.  
11726492 E.Warkentin, B.Mamat, M.Sordel-Klippert, M.Wicke, R.K.Thauer, M.Iwata, S.Iwata, U.Ermler, and S.Shima (2001).
Structures of F420H2:NADP+ oxidoreductase with and without its substrates bound.
  EMBO J, 20, 6561-6569.
PDB codes: 1jax 1jay
  11489939 P.T.Clayton, S.Eaton, A.Aynsley-Green, M.Edginton, K.Hussain, S.Krywawych, V.Datta, H.E.Malingre, R.Berger, and I.E.van den Berg (2001).
Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion.
  J Clin Invest, 108, 457-465.  
10841783 R.E.Campbell, S.C.Mosimann, I.van De Rijn, M.E.Tanner, and N.C.Strynadka (2000).
The first structure of UDP-glucose dehydrogenase reveals the catalytic residues necessary for the two-fold oxidation.
  Biochemistry, 39, 7012-7023.
PDB codes: 1dli 1dlj
  10548046 J.J.Barycki, L.K.O'Brien, J.J.Birktoft, A.W.Strauss, and L.J.Banaszak (1999).
Pig heart short chain L-3-hydroxyacyl-CoA dehydrogenase revisited: sequence analysis and crystal structure determination.
  Protein Sci, 8, 2010-2018.
PDB code: 3hdh
10531522 M.A.Walsh, G.Evans, R.Sanishvili, I.Dementieva, and A.Joachimiak (1999).
MAD data collection - current trends.
  Acta Crystallogr D Biol Crystallogr, 55, 1726-1732.  
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.