PDBsum entry: 1i7k

Ligase

PDB id: 1i7k

Contents

Protein chains

146 a.a. *

Waters ×196

* Residue conservation analysis

PDB id:

1i7k

Name:

Ligase

Title:

Crystal structure of human mitotic-specific ubiquitin- conjugating enzyme, ubch10

Structure:

Ubiquitin-conjugating enzyme e2 h10. Chain: a, b. Synonym: ubiquitin-conjugating enzyme ubch10. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ubch10. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.95Å R-factor: 0.176 R-free: 0.226

Authors:

R.Basavappa,Y.Lin

Key ref:

Y.Lin et al. (2002). Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10. J Biol Chem, 277, 21913-21921. PubMed id: 11927573 DOI: 10.1074/jbc.M109398200

Date:

09-Mar-01 Release date: 04-Apr-01

Protein chains

O00762  (UBE2C_HUMAN) -  Ubiquitin-conjugating enzyme E2 C

Seq: 179 a.a.

Struc: 146 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.6.3.2.19 - Ubiquitin--protein ligase.
• Reaction: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: cytosol (3 terms)
• Biological process: cell cycle (19 terms)
• Biochemical function: nucleotide binding (6 terms)

reference

DOI no: 10.1074/jbc.M109398200

J Biol Chem 277:21913-21921 (2002)

PubMed id: 11927573

Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10.

Y.Lin, W.C.Hwang, R.Basavappa.

ABSTRACT

Cell cycle progression is controlled at several different junctures by the targeted destruction of cell cycle regulatory proteins. These carefully orchestrated events include the destruction of the securin protein to permit entry into anaphase, and the destruction of cyclin B to permit exit from mitosis. These destruction events are mediated by the ubiquitin/proteasome system. The human ubiquitin-conjugating enzyme, UbcH10, is an essential mediator of the mitotic destruction events. We report here the 1.95-A crystal structure of a mutant UbcH10, in which the active site cysteine has been replaced with a serine. Functional analysis indicates that the mutant is active in accepting ubiquitin, although not as efficiently as wild-type. Examination of the crystal structure reveals that the NH2-terminal extension in UbcH10 is disordered and that a conserved 3(10)-helix places a lysine residue near the active site. Analysis of relevant mutants demonstrates that for ubiquitin-adduct formation the presence or absence of the NH2-terminal extension has little effect, whereas the lysine residue near the active site has significant effect. The structure provides additional insight into UbcH10 function including possible sites of interaction with the anaphase promoting complex/cyclosome and the disposition of a putative destruction box motif in the structure.

Selected figure(s)

Figure 5.
Fig. 5. The 3[10] helix situated near the active site (divergent stereoview). The molecular surface was calculated using all residues except those in the 3[10] helix (residues 115-119). The residues forming the 3[10] helix are shown in ball-and-stick representation. The geometry of the 3[10] helix allows the hydrophobic residues in the helix to pack primarily against non-polar interior residues, whereas the hydrophilic residues are substantially solvent exposed. The polar residue Lys119 is seen to be proximal to the active site thiol (indicated by the dark patch). The small inset -carbon trace shows the overall perspective from which the main figure was made. The 3[10] helix and active site residue are indicated by thicker segments.

Figure 7.
Fig. 7. Candidate sites of interaction with the APC/C. The relative positions of the active site ( red) and the likely site of APC11 interaction (residues Tyr91 and Ala^124) are shown in the left figure. The right figure is related to the left figure by a rotation of 180° about a vertical axis in the plane of the paper. The colored and labeled patches are residues that are conserved only among mitotic Ubcs. The color coding is as follows: red, blue, yellow, and brown correspond to acidic, basic, polar, and hydrophobic residues, respectively. Green indicates the active site cysteine.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 21913-21921) copyright 2002.

Figures were selected by an automated process.