Structural Biochemistry/Enzyme/FeMo Cofactor and FeFe-Hydrogenase
FeMo Cofactor and FeFe-HydrogenaseEdit
FeMo Cofactor and FeFe-Hydrogenase are the enzymes with unique complex iron-surfur at their active site. They are used for nucleotide binding and hydrolysis. In order to synthesize properly and be inserted in to the structural enzymes, they need specific maturation machinery.
The iron-sulfur clusters are the active site of both FeMo cofactor and FeFe-Hydrogenase. They are metal cofactors which exist as diver form such as [2Fe-2S], [4Fe-4S], [3Fe-4S]. They not only meditate electron transfer, gene expression, and catalysis but also play critical roles in central metabolic process such as respiration, photosynthesis, and the catalytic interconversion of small molecules. Each clusters has different protein environment. For example, the iron in the [2Fe-2S] cluster is coordinated with two cysteine thiolates and in the [4Fe-4S] cluster, each iron is coordinated with one cysteine. The different protein environments influence on the redox potential of the clusters.
1. They are Modular inorganic/organometallic nanocrystals
2. 2Fe subcluster has only minimal protein coordination and possess unusual protein ligands that influence on the reactivity of the cluster
Nitrogenase FeMo cofactor (iron-Molybdenum (FeMo) cofactor at the active site of nitrogenase)Edit
Nitrogenase FeMo cofactor is a hetero metallic cluster that is [4Fe-3S] partial cubane fused to [Mo-3Fe-4S] partial cubane through three cubane bridging sulfides. It has nonprotein ligands and a homocitrate which coordinates the Mo via hydroxyl and carbocylate moieties or coordinates all six Fe ions of the cofactor core.
It is a process which nitrogen is converted to ammonia. It plays a major role in nitrogen cycling, and Its availability of fixed nitrogen is a limiting factor for global nutrition. Also, it is catalyzed by nitrogenase enzyme which is not expressed by eukaryotes. The form which contains heterometal independent, Mo-nitrogenase is the most common.
FeMo cofactor is located in the core of the active site of the Mo-nitrogenase and takes part in catalyzing the reduction of N2 to NH3, which has high activation energy. Mo nitrogenase is composed of two proteins, the Fe protein and the MoFe protein. During the catalysis, two proteins associate and dissociate in order to couple nucleotide binding and hydrolysis to intermolecular electron transfer from the [4Fe-4S] to the FeMo cofactor active site in charge of P cluster
Synthesis of Iron-Sulfur clusterEdit
The involvement of FeS cluster is a precursor to the complex cluster. In order to bring S and Fe together to produce simple [2Fe-2S] and [4Fe-4S] clusters, NifS and NifU are used. For the iron-sulfur cluster assembly, the Isc and Suf pathways are involved. The Isc machinery includes IscU, assembles iron and sulfide, and makes [2Fe-2S] and [4Fe-4S] clusters. After the assembly, it delivers the clusters to target proteins. In the Suf machinery, proteins SufU and SufA serve as assembly scaffold and delivers the cluster to target proteins. In the process of assembly, a source of electros is required. In the case of Isc system, sulfur is reduced or two [2Fe2S] is fused to form a [4Fe-4S] on IscU. There is also a chaperon system, which is composed of HscA ATPase and cochaperone HscB in the Isc macinery. The HscA interacts with a motif on IscU in order to transfer the cluster from IscU to the target protein.
synthesis of the FeMo cofactor occurs on the NifEN heterotetramer that carries out nitrogenase maturation and incorporation of iron, molybdenum, and homocitrate into the FeMo-cofactor precursor. NifEN scaffold interacts with NifB and NifH. NifEN, NifB, and NifH play a major role in synthesizing the FeMo cofactor.
Hydrogenase H clusterEdit
Hydrogenase H cluster is composed of a diiron cluster with unusual nonprotein ligands bridges to a [4Fe-4S] cluster. In the [4Fe-4S] subcluster, one of the coordinating cysteine thiolates bridge between [4Fe-4S] subcluster and the 2Fe subcluster, which each Fe ion in the cluster is coordinated by terminal carbon monoxide and cyanide ligands with an additional Fe-bridging carbon monoxide ligand. They are two enzymes that take part in Hydrogen metabolism ; [NiFe]-Hydrogenases that are related to bacteria and archaea, and [FeFe]- hydrogenases that are found in bacteria, protists, and green algae. Both of them function either in hydrogen oxidation coupled to energy yielding reaction or in recycling reduced-electron carriers. They have a specific active-site domain or subunit containing the H cluster or heterobimetallic NiFe centers.