Please contact us for any questions or request for reagents for this structure.

MGC35130 (SGC Target ID UBC53) - Human Ubiquitin-Conjugating Enzyme of Unknown Function

PDB entry: 1YRV

can not load file:

MGC35130 is one of the most divergent members of the E2 family, containing a minimum number of conserved residues. All conserved amino acids except the nucleophilic cysteine are core residues. The domain fold of MGC35130 is clearly that of the ubiquitin conjugase family, but while the amino terminal secondary structural elements align very well with other members, the carboxyl terminal helices (helix-A3 and A4) are positioned significantly away from the conserved position. The large side chain of Tyrosine-140 contributes to the packing of helix-A4, and may be responsible for the tertiary structure divergence.

The human genome contains numerous genes encoding ubiquitin-like proteins as well as about forty genes for ubiquitin-conjugating proteins. One of the more intriguing questions concerns specificity, namely, which ubiquitin homolog binds to which conjugating protein(s). As an approach to solving this problem, we aim to determine the structures of all human ubiquitin-conjugating proteins.

With the notion that conjugases interact with their corresponding ubiquitin homologs through a mechanism similar to yeast UBC1 (Hamilton et. al., 2001), the ubiquitin binding surface of MGC35130 is expected to be composed of the loop connecting B2 and B3, helix-A2, and the coiled regions just prior to and following helix-A2. Consistent with other ubiquitin conjugating proteins, this surface is relatively flat. The solvent exposed surface of helix-A2, which contributes the largest surface area for interaction with ubiquitin, contains three aliphatic side chains, an asparigine, a serine, and tyrosine that could contribute to direct interactions with corresponding ubiquitin homologs. The coiled regions prior to and following helix-A2 contain glutamates and aspartates that may act as general acids to the ubiquitination and deubiquitination reaction. The amino terminal coiled region, prior to helix-A2, contains a lysine residue that could complement an acid group of the corresponding ubiquitin homolog. In addition, the loop connecting strand-B2 and B3 contains a glutamic acid that could complement a basic residue on corresponding ubiquitin homologs.

Materials and Methods