[NiFeSe] hydrogenase

 

[NiFeSe] hydrogenases are metalloenzymes that catalyze the reaction H2 ↔ 2H+ + 2e-. They are generally heterodimeric, contain three iron–sulfur clusters in their small subunit and a nickel–iron-containing active site in their large subunit that includes a selenocysteine (SeCys) ligand.

 

Reference Protein and Structure

Sequences
P13065 UniProt (1.12.99.6)
P13063 UniProt (1.12.99.6) IPR001501,IPR001821 (Sequence Homologues) (PDB Homologues)
Biological species
Desulfomicrobium baculatum (Bacteria) Uniprot
PDB
1cc1 - CRYSTAL STRUCTURE OF A REDUCED, ACTIVE FORM OF THE NI-FE-SE HYDROGENASE FROM DESULFOMICROBIUM BACULATUM (2.15 Å) PDBe PDBsum 1cc1
Catalytic CATH Domains
1.10.645.10 CATHdb 4.10.480.10 CATHdb 3.40.50.700 CATHdb (see all for 1cc1)
Cofactors
Tetra-mu3-sulfido-tetrairon (3), Carbonmonoxide-(dicyano) iron (1), Nickel(2+) (1)
Click To Show Structure

Enzyme Reaction (EC:1.12.99.6)

dihydrogen
CHEBI:18276ChEBI
+
acceptor
CHEBI:15339ChEBI
→
hydrogen donor
CHEBI:17499ChEBI
Alternative enzyme names: H(2) producing hydrogenase, Hydrogen-lyase, Hydrogenlyase, Uptake hydrogenase, Hydrogen:(acceptor) oxidoreductase,

Enzyme Mechanism

Introduction

The reaction proceeds as follows:

  1. Electron transfer from an electron transport protein to [4Fe-4S] cluster-3 located on the surface of small subunit
  2. Electron transfer from [4Fe-4S] cluster-3 to [4Fe-4S] cluster-2
  3. Electron transfer from [4Fe-4S] cluster-2 to [4Fe-4S] cluster-1
  4. Electron transfer from [4Fe-4S] cluster-1 to the Nickel-Iron cluster (primary active site)
  5. Hydrogenation at the Nickel-Iron cluster (primary active site)

Catalytic Residues Roles

UniProt PDB* (1cc1)
Cys71 Cys70L(B) Acts as one of the metal centre binding ligands. metal ligand
His240, Cys243, Cys269, Cys263 His208S(A), Cys211S(A), Cys237S(A), Cys231S(A) Forms binding site of the distal Fe4S4 cluster. metal ligand
Sec493 Sec492L(B) Involved in the mediation of the heterolytic cleavage of molecular hydrogen, along with the nickel centre. It is also involved in protecting the nickel atom from oxidation. activator, metal ligand
Cys290, Cys278, Cys296, Cys299 Cys258S(A), Cys246S(A), Cys264S(A), Cys267S(A) Forms binding site for the medial Fe4S4 cluster. metal ligand
Arg426 Arg425L(B) Involved in the electrostatic stabilisation of the cofactor, forms hydrogen bonds with the proximal C#N group and the selenosysteine residue. electrostatic stabiliser
Cys158, Cys196, Cys50, Cys53 Cys126S(A), Cys164S(A), Cys18S(A), Cys21S(A) Forms the binding site of the proximal Fe4S4 cluster. metal ligand
Cys74, Cys496 Cys73L(B), Cys495L(B) Acts as the bridging ligands between the Ni(II) and Fe(II) centres. metal ligand
His78 His77L(B) Acts as a general acid/base to shuttle the protons into and out of the active site. proton shuttle (general acid/base)
Glu24 Glu23L(B) Possible general acid/base proton shuttle (general acid/base)
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Wombwell C et al. (2015), Acc Chem Res, 48, 2858-2865. [NiFeSe]-Hydrogenase Chemistry. DOI:10.1021/acs.accounts.5b00326. PMID:26488197.
  2. Vedha SA et al. (2016), RSC Adv, 6, 81636-81646. Noncovalent interactions between the second coordination sphere and the active site of [NiFeSe] hydrogenase. DOI:10.1039/c6ra11295a.
  3. Vedha SA et al. (2015), Phys Chem Chem Phys, 17, 20677-20686. Insights from the computational studies on the oxidized as-isolated state of [NiFeSe] hydrogenase from D. vulgaris Hildenborough. DOI:10.1039/c5cp03071d. PMID:26205195.
  4. Ceccaldi P et al. (2015), Chem Commun (Camb), 51, 14223-14226. Oxidative inactivation of NiFeSe hydrogenase. DOI:10.1039/c5cc05930e. PMID:26260963.
  5. Wombwell C et al. (2014), Dalton Trans, 43, 4483-4493. Synthesis, structure and reactivity of Ni site models of [NiFeSe] hydrogenases. DOI:10.1039/c3dt52967c. PMID:24366040.
  6. Marques MC et al. (2013), Int J Hydrogen Energy, 38, 8664-8682. Redox state-dependent changes in the crystal structure of [NiFeSe] hydrogenase from Desulfovibrio vulgaris Hildenborough. DOI:10.1016/j.ijhydene.2013.04.132.
  7. Nonaka K et al. (2013), J Biosci Bioeng, 115, 366-371. Novel H2-oxidizing [NiFeSe]hydrogenase from Desulfovibrio vulgaris Miyazaki F. DOI:10.1016/j.jbiosc.2012.10.011. PMID:23201506.
  8. Volbeda A et al. (2013), Chem Commun (Camb), 49, 7061-. Structural foundations for the O2 resistance of Desulfomicrobium baculatum [NiFeSe]-hydrogenase. DOI:10.1039/c3cc43619e. PMID:23811828.
  9. Baltazar CS et al. (2012), J Biol Inorg Chem, 17, 543-555. Structural features of [NiFeSe] and [NiFe] hydrogenases determining their different properties: a computational approach. DOI:10.1007/s00775-012-0875-2. PMID:22286956.
  10. Baltazar CSA et al. (2011), Eur J Inorg Chem, 2011, 948-962. Nickel-Iron-Selenium Hydrogenases - An Overview. DOI:10.1002/ejic.201001127.
  11. Marques MC et al. (2010), J Mol Biol, 396, 893-907. The Three-Dimensional Structure of [NiFeSe] Hydrogenase from Desulfovibrio vulgaris Hildenborough: A Hydrogenase without a Bridging Ligand in the Active Site in Its Oxidised, “as-Isolated” State. DOI:10.1016/j.jmb.2009.12.013. PMID:20026074.
  12. Gutiérrez-Sánchez C et al. (2010), J Biol Inorg Chem, 15, 1285-1292. Interaction of the active site of the Ni–Fe–Se hydrogenase from Desulfovibrio vulgaris Hildenborough with carbon monoxide and oxygen inhibitors. DOI:10.1007/s00775-010-0686-2. PMID:20669037.
  13. De Lacey AL et al. (2008), J Biol Inorg Chem, 13, 1315-1320. FTIR spectroelectrochemical characterization of the Ni–Fe–Se hydrogenase from Desulfovibrio vulgaris Hildenborough. DOI:10.1007/s00775-008-0412-5. PMID:18704522.
  14. Parkin A et al. (2008), J Am Chem Soc, 130, 13410-13416. The Difference a Se Makes? Oxygen-Tolerant Hydrogen Production by the [NiFeSe]-Hydrogenase fromDesulfomicrobium baculatum. DOI:10.1021/ja803657d. PMID:18781742.
  15. Valente FM et al. (2005), J Biol Inorg Chem, 10, 667-682. Hydrogenases in Desulfovibrio vulgaris Hildenborough: structural and physiologic characterisation of the membrane-bound [NiFeSe] hydrogenase. DOI:10.1007/s00775-005-0022-4. PMID:16187073.
  16. Stein M et al. (2001), Phys Chem Chem Phys, 3, 5115-5120. The electronic structure of the catalytic intermediate Ni-C in [NiFe] and [NiFeSe] hydrogenasesElectronic Supplementary Information available. See http://www.rsc.org/suppdata/cp/b1/b105723p/. DOI:10.1039/b105723p.
  17. Garcin E et al. (1999), Structure, 7, 557-566. The crystal structure of a reduced [NiFeSe] hydrogenase provides an image of the activated catalytic center. DOI:10.1016/s0969-2126(99)80072-0. PMID:10378275.

Step 1.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Cys18S(A) metal ligand
Cys21S(A) metal ligand
Cys126S(A) metal ligand
Cys164S(A) metal ligand
His208S(A) metal ligand
Cys211S(A) metal ligand
Cys237S(A) metal ligand
Cys231S(A) metal ligand
Cys246S(A) metal ligand
Cys258S(A) metal ligand
Cys264S(A) metal ligand
Cys267S(A) metal ligand
Cys70L(B) metal ligand
Cys73L(B) metal ligand
Sec492L(B) metal ligand, activator
Cys495L(B) metal ligand
His77L(B) proton shuttle (general acid/base)
Arg425L(B) electrostatic stabiliser
Glu23L(B) proton shuttle (general acid/base)

Chemical Components

Step 1.

Contributors

Nozomi Nagano, Gemma L. Holliday