Sepiapterin reductase deficiency is caused by mutations in the spr gene and is inherited as an autosomal recessive disorder. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. Cloning of mouse sepiapterin reductase gene and characterization of its promoter region article pdf available in biochimica et biophysica acta bba gene structure and expression 14451. It contributes to better recognition of the clinical pattern of sepiapterin reductase deficiency. Sepiapterin reductase deficiency srd is an underrecognized levodoparesponsive disorder. Crystal structure of human sepiapterin reductase in complex with an n acetylserotinin analogue. Sepiapterin reductase catalyses the last steps in the biosynthesis of. Teacher notes, student handouts and interactive jmol visualization tools are available online. Mutations in this gene result in doparesponsive dystonia due to sepiaterin reductase deficiency. Jmol quick reference sheet a jmol quick reference sheet that highlights key commands and useful resources for designing protein models in jmol on one side and a clear chart of the 20 amino acids on the other side. Sepiapterin reductase is an enzyme that in humans is encoded by the spr gene. Sulfa drugs inhibit sepiapterin reduction and chemical redox. However, thus far, enzyme activity of spr in musca domestica is kept unknown. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Important connections enzymes that require tetrahydrobiopterin are important for the production of amino acids, but perhaps their most visible role is in the production of neurotransmitters. Disease description a form of doparesponsive dystonia. New inhibitors of sepiapterin reductase lack of an effect of intracellular tetrahydrobiopterin depletion upon in vitro proliferation of two human cell lines received for publication, august 22,1991 gary k. It was first described in silkworms where it was shown to be a separate enzyme from dihydrofolate reductase matsubara et al. Targeting sepiapterin reductase to treat neuropathic pain. Sepiapterin reductase elisa kits 7 sepiapterin reductase spr elisa kits from 4 manufacturers are available on. Other movement problems can include muscle stiffness spasticity, tremors, problems with coordination and balance ataxia, and involuntary jerking movements chor. Search chemicals by name, molecular formula, structure, and other identifiers. The new mutation in sepiapterin reductase sr is likely to impair transcription processing and cause deficiencies in sepiapterin reductase, thus decreasing levels of bh 4 and dopa. Pdf cloning of mouse sepiapterin reductase gene and.
Sepiapterin reductase mediates chemical redox cycling in lung. After years of extremely limited mobility, severe breathing problems, costly emergency department visits, imaging tests, and visits to specialists, genome sequencing identified mutations in a gene called spr that encodes the enzyme sepiapterin reductase. Studies on spr from several insects and other organisms have been reported. Sepiapterin reductase deficiency is a rare condition. Protein modeling event prebuild design environment msoe. Sepiapterin reductase deficiency srd often presents with nonspecific symptoms including global delay with hypotonia or a nonspecific gait disorder, often with cognitive impairment. In the majority of cases, patients manifest progressive psychomotor retardation, dystonia and spasticity.
Sepiapterin reductase deficiency genetic and rare diseases. Apr 19, 2016 sepiapterin reductase deficiency is caused by mutations in the spr gene. Sepiapterin reductase deficiency is a treatable neurometabolic condition. Spr also mediates chemical redox cycling, catalyzing oneelectron reduction of redoxactive chemicals, including quinones and bipyridinium herbicides e. The purpose of the jmol exploration component of this years event is to allow students to demonstrate their skill in using jmol to manipulate and explore a pdb file, and navigate the rcsb protein data bank website.
Sepiapterin reductase deficiency genetics home reference nih. Biology 490 molecular biology university of san diego. Spr gene mutations disrupt the production of sepiapterin reductase. Sepiapterin reductase spr catalyzes the final steps of bh4 biosynthesis. As a member of the wwpdb, the rcsb pdb curates and annotates pdb data according to agreed upon standards. Jun 22, 2015 in this video, alban latremoliere, michael costigan, and clifford woolf describe how they genetically manipulated the tetrahydrobiopterin synthesis pathway in mice to formally validate its role in. Sepiapterin reductase deficiency is an inherited pediatric disorder characterized by movement problems, and most commonly displayed as a pattern of involuntary sustained muscle contractions known as dystonia. Tetrahydrobiopterin bh4 is an essential cofactor for aromatic acid hydroxylases and nitric oxide synthase. Sepiapterin reductase and alr2 aldose reductase from. Click here to download the entire sepiapterin reductase gene as a pdf document. The mechanism for absence of hyperphenylalaninemia is the existence of aldose reductase, carbonyl reductase, and dihydrofolate reductase in the liver but not the cns, allowing phenylalanine hydroxylation via peripheral conversion of sepiapterin to bh 4 39,61. We have determined the crystal structure of mouse sepiapterin reductase by multiple.
Hyperreflexia andor striatal toe simulating a babinski reflex but without fanning of the toes may be present. Sepiapterin reductase how is sepiapterin reductase abbreviated. How can i model cas9 and cytidine deaminase in one jmol file. Expression and enzyme activity detection of a sepiapterin. Jul 01, 2015 the phenotypic spectrum of sepiapterin reductase deficiency srd, which ranges from significant motor and cognitive deficits to only minimal findings, has not been completely elucidated. Dopamine and serotonin biosynthesis models and sepiapterin. Mouse and chlorobium bacteria sepiapterin reductases 9. Link to this years theme webpage, which has both papers available to download in tab 3. Since the original description, 14 cases of sepiapterin reductase deficiency have been described or collected in the database 1,2,47. The rcsb pdb also provides a variety of tools and resources. Sepiapterin reductase an overview sciencedirect topics.
Sulfa drugs inhibit sepiapterin reduction and chemical redox cycling by sepiapterin reductase shaojun yang, yihua jan, vladimir mishin, jason r. It should be considered in patients with motorcognitive delay, dystonia, or oculogyric crisis. Sepiapterin reductase catalyzes the final step in the biosynthetic pathway of tetrahydrobiopterin bh 4, an essential cofactor for aromatic amino acid hydrolases including tyrosine hydroxylase, the ratelimiting enzyme in dopamine synthesis. Spr plays an important role in the biosynthesis of tetrahydrobiopterin bh4. Here you can see if sepiapterin reductase deficiency can be hereditary. At least 30 cases have been described in the scientific literature. Use and redistribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material hmdb and the original publication see the hmdb citing page. Spr sepiapterin reductase homo sapiens human spr gene. We describe clinical, biochemical, and molecular findings in a cohort of patients with this treatable. Sepiapterin reductase deficiency genetics home reference. Defects in spr are the cause of dystonia doparesponsive due to sepiapterin reductase deficiency drdsprd mim.
Developedbythemilwaukeeschoolofengineeringcenterfor biomolecularmodeling. As with segawa disease, it too requires analysis of csf for diagnosis. Most spr gene mutations result in an enzyme with little or no function. Oct 12, 2019 this gene encodes an aldoketo reductase that catalyzes the nadphdependent reduction of pteridine derivatives and is important in the biosynthesis of tetrahydrobiopterin bh4. The role of sepiapterin reductase in the biosynthesis of two. Screening of a novel fragment library with functional complexity against mycobacterium tuberculosis inha.
Sepiapterin reductase and the beery twins cbm science. Pubchem is the worlds largest collection of freely accessible chemical information. Cbm science olympiad biological significance msoe center. Hmdb is offered to the public as a freely available resource. Targeting sepiapterin to block bh4induced chronic pain. Finally, the enzyme sepiapterin reductase sr, pdb entry 1sep cleans up the portion of the sugar that is left to form the final cofactor. One candidate gene at this locus is sepiapterin reductase spr. The clinical phenotype of recessive sepiapterin reductase deficiency includes progressive psychomotor retardation with onset in the first year of life. A nonfunctional sepiapterin reductase leads to a lack of tetrahydrobiopterin and a decrease in the production of dopamine and serotonin in the brain. Sepiapterin reductase deficiency can be classified as a form of dystonia, a pediatric neurotransmitter disorder or a disorder of tetrahydrobiopterin deficiency. Find chemical and physical properties, biological activities, safety and toxicity information, patents, literature citations and more. Sepiapterin reductase deficiency is a condition characterized by movement problems, most often a pattern of involuntary, sustained muscle contractions known as dystonia. Diagnosis is based on specific and careful examination of neurotransmitter metabolites in the cerebrospinal fluid csf via lumbar puncture.
Jun 17, 2015 the study published today underscores sepiapterin reductase as an attractive drug target for the development of a potentially safe and efficacious treatment for chronic pain and inflammation, said kevin pojasek, phd, quartets president and acting chief executive officer, in a press release. This gene provides instructions for making the sepiapterin reductase enzyme, which is involved in the productions of a molecule called tetrahydrobiopterin also known as bh4. Does any member of your family have sepiapterin reductase deficiency or may be more predisposed to developing the condition. Other movement problems can include muscle stiffness spasticity, tremors, problems with coordination and balance ataxia, and involuntary jerking movements chorea. Sepiapterin reductase proteins 19 sepiapterin reductase spr proteins from 9 manufacturers are available on. Sepiapterin reductase deficiency srd is a dopasensitive neurotransmitter disorder, caused by mutation of the spr gene located on chromosome 2p14p12.
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