SDHB

639067680ENSG00000117118ENSMUSG00000009863P21912Q9CQA3NM_003000NM_023374NM_001355515NP_002991NP_075863NP_001342444Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB) also known as iron-sulfur subunit of complex II (Ip) is a protein that in humans is encoded by the SDHB gene.2h89: Avian Respiratory Complex II with Malonate Bound1zp0: Crystal Structure of Mitochondrial Respiratory Complex II bound with 3-nitropropionate and 2-thenoyltrifluoroacetone1yq4: Avian respiratory complex ii with 3-nitropropionate and ubiquinone2fbw: Avian respiratory complex II with carboxin bound1zoy: Crystal Structure of Mitochondrial Respiratory Complex II from porcine heart at 2.4 Angstroms1yq3: Avian respiratory complex ii with oxaloacetate and ubiquinone2h88: Avian Mitochondrial Respiratory Complex II at 1.8 Angstrom Resolution Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB) also known as iron-sulfur subunit of complex II (Ip) is a protein that in humans is encoded by the SDHB gene. The succinate dehydrogenase (also called SDH or Complex II) protein complex catalyzes the oxidation of succinate (succinate + ubiquinone => fumarate + ubiquinol). SDHB is one of four protein subunits forming succinate dehydrogenase, the other three being SDHA, SDHC and SDHD. The SDHB subunit is connected to the SDHA subunit on the hydrophilic, catalytic end of the SDH complex. It is also connected to the SDHC/SDHD subunits on the hydrophobic end of the complex anchored in the mitochondrial membrane. The subunit is an iron-sulfur protein with three iron-sulfur clusters. It weighs 30 kDa. The gene that codes for the SDHB protein is nuclear, not mitochondrial DNA. However, the expressed protein is located in the inner membrane of the mitochondria. The location of the gene in humans is on the first chromosome at locus p36.1-p35. The gene is coded in 1,162 base pairs, partitioned in 8 exons. The expressed protein weighs 31.6 kDa and is composed of 280 amino acids. SDHB contains the iron-sulphur clusters necessary for tunneling electrons through the complex. It is located between SDHA and the two transmembrane subunits SDHC and SDHD. The SDH complex is located on the inner membrane of the mitochondria and participates in both the Citric Acid Cycle and Respiratory chain. SDHB acts as an intermediate in the basic SDH enzyme action shown in Figure 1: Initially, SDHA oxidizes succinate via deprotonation at the FAD binding site, forming FADH2 and leaving fumarate, loosely bound to the active site, free to exit the protein. Electrons from FADH2 are transferred to the SDHB subunit iron clusters ,, and tunnel along the relay until they reach the iron sulfur cluster. The electrons are then transferred to an awaiting ubiquinone molecule at the Q pool active site in the SDHC/SDHD dimer. The O1 carbonyl oxygen of ubiquinone is oriented at the active site (image 4) by hydrogen bond interactions with Tyr83 of SDHD. The presence of electrons in the iron sulphur cluster induces the movement of ubiquinone into a second orientation. This facilitates a second hydrogen bond interaction between the O4 carbonyl group of ubiquinone and Ser27 of SDHC. Following the first single electron reduction step, a semiquinone radical species is formed. The second electron arrives from the cluster to provide full reduction of the ubiquinone to ubiquinol. Germline mutations in the gene can cause familial paraganglioma (in old nomenclature, Paraganglioma Type PGL4). The same condition is often called familial pheochromocytoma. Less frequently, renal cell carcinoma can be caused by this mutation.