4ii2

Crystal structure of Ubiquitin activating enzyme 1 (Uba1) in complex with the Ub E2 Ubc4, ubiquitin, and ATP/MgCrystal structure of Ubiquitin activating enzyme 1 (Uba1) in complex with the Ub E2 Ubc4, ubiquitin, and ATP/Mg

Structural highlights 4ii2 is a 3 chain structure with sequence from Schizosaccharomyces pombe 972h-. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , , Related: 4ii3 Gene: ptr3, SPBC1604.21c, SPBC211.09, Ubiquitin activating enzyme 1 (Uba1) (Schizosaccharomyces pombe 972h-), ubi2 (Schizosaccharomyces pombe 972h-), SPBC119.02, ubc4, Ubiquitin conjugating enzyme 4 (Ubc4) (Schizosaccharomyces pombe 972h-) Activity: Ubiquitin--protein ligase, with EC number 6.3.2.19 Resources: FirstGlance, OCA, RCSB, PDBsum Function [UBA1_SCHPO] Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding an ubiquitin-E1 thioester and free AMP. [UBC4_SCHPO] Catalyzes the covalent attachment of ubiquitin to other proteins. Mediates the selective degradation of short-lived and abnormal proteins. Mediates ubiquitination of PEX5 (By similarity). [RL402_SCHPO] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, and DNA-damage responses. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Ribosomal protein L40 is a component of the 60S subunit of the ribosome. Publication Abstract from PubMed Ubiquitin (Ub) conjugation is initiated by an E1 enzyme that catalyzes carboxy-terminal Ub adenylation, thioester bond formation to a catalytic cysteine in the E1 Cys domain, and thioester transfer to a catalytic cysteine in E2 conjugating enzymes. How the E1 and E2 active sites come together during thioester transfer and how Ub E1 interacts with diverse Ub E2s remains unclear. Here we present a crystal structure of a Ub E1-E2(Ubc4)/Ub/ATPMg complex that was stabilized by induction of a disulfide bond between the E1 and E2 active sites. The structure reveals combinatorial recognition of the E2 by the E1 ubiquitin-fold domain (UFD) and Cys domain and mutational analysis, coupled with thioester transfer assays with E1, Ubc4, and other Ub E2s, show that both interfaces are important for thioester transfer. Comparison to a Ub E1/Ub/ATPMg structure reveals conformational changes in the E1 that bring the E1 and E2 active sites together. Structure of a ubiquitin e1-e2 complex: insights to e1-e2 thioester transfer.,Olsen SK, Lima CD Mol Cell. 2013 Mar 7;49(5):884-96. doi: 10.1016/j.molcel.2013.01.013. Epub 2013, Feb 14. PMID:23416107 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosomal protein L40 Ubiquitin activating enzyme Ubiquitin conjugating enzyme

spinqualitylabelsall models 4ii2, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image