2pid
From Proteopedia
Crystal structure of human mitochondrial tyrosyl-tRNA synthetase in complex with an adenylate analog
Structural highlights
Disease[SYYM_HUMAN] Defects in YARS2 are the cause of myopathy with lactic acidosis and sideroblastic anemia type 2 (MLASA2) [MIM:613561]. MLASA2 is a rare oxidative phosphorylation disorder specific to skeletal muscle and bone marrow. Affected individuals manifest sideroblastic anemia, progressive lethargy, muscle weakness, and exercise intolerance associated with persistent lactic acidemia.[1] [2] Function[SYYM_HUMAN] Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) (By similarity).[3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe report the structure of a strictly mitochondrial human synthetase, namely tyrosyl-tRNA synthetase (mt-TyrRS), in complex with an adenylate analog at 2.2 A resolution. The structure is that of an active enzyme deprived of the C-terminal S4-like domain and resembles eubacterial TyrRSs with a canonical tyrosine-binding pocket and adenylate-binding residues typical of class I synthetases. Two bulges at the enzyme surface, not seen in eubacterial TyrRSs, correspond to conserved sequences in mt-TyrRSs. The synthetase electrostatic surface potential differs from that of other TyrRSs, including the human cytoplasmic homolog and the mitochondrial one from Neurospora crassa. The homodimeric human mt-TyrRS shows an asymmetry propagating from the dimer interface toward the two catalytic sites and extremities of each subunit. Mutagenesis of the catalytic domain reveals functional importance of Ser200 in line with an involvement of A73 rather than N1-N72 in tyrosine identity. Crystal structure of human mitochondrial tyrosyl-tRNA synthetase reveals common and idiosyncratic features.,Bonnefond L, Frugier M, Touze E, Lorber B, Florentz C, Giege R, Sauter C, Rudinger-Thirion J Structure. 2007 Nov;15(11):1505-16. PMID:17997975[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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