Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.2.19 (ubiquitin-protein ligase)
 799 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since its discovery in 1981, ubiquitin-activating enzyme 1 was thought to be the only E1-type enzyme responsible for ubiquitin activation. Recently, a relatively uncharacterized E1 enzyme, designated ubiquitin-like modifier activating enzyme 6, was also shown to activate ubiquitin. Ubiquitin-activating enzyme 1 and ubiquitin-like modifier activating enzyme 6 are both essential proteins, and each uses a different spectrum of ubiquitin-conjugating (E2) enzymes. Ubiquitin-like modifier activating enzyme 6 activates not only ubiquitin, but also the ubiquitin-like modifier FAT10 (human leukocyte antigen F-associated transcript 10), which, similarly to ubiquitin, serves as a signal for proteasomal degradation. This new layer of regulation in ubiquitin activation markedly increases the versatility of the ubiquitin conjugation system.
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PMID:Activating the ubiquitin family: UBA6 challenges the field. 1835 50

Ubiquitin-activating enzyme (E1) is a key regulator in protein ubiquitination, which lies on the upstream of the ubiquitin-related pathways and determines the activation of the downstream enzyme cascade. Thus far, no structural information about the human ubiquitin-activating enzyme has been reported. We expressed and purified the N-terminal domains of human E1 and determined their crystal structures, which contain inactive adenylation domain (IAD) and the first catalytic cysteine half-domain (FCCH). This study presents the crystal structure of human E1 fragment for the first time. The main structure of both IAD and FCCH superimposed well with their corresponding domains in yeast Uba1, but their relative positions vary significantly. This work provides new structural insights in understanding the mechanisms of ubiquitin activation in humans.
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PMID:Expression, purification, and crystal structure of N-terminal domains of human ubiquitin-activating enzyme (E1). 2520 2