PDBsum entry 3cmm

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Ligase/protein binding PDB id
Protein chains
1001 a.a. *
76 a.a. *
PRO ×2
Waters ×176
* Residue conservation analysis
PDB id:
Name: Ligase/protein binding
Title: Crystal structure of the uba1-ubiquitin complex
Structure: Ubiquitin-activating enzyme e1 1. Chain: a, c. Fragment: residues 10-1024. Engineered: yes. Ubiquitin. Chain: b, d. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Gene: uba1. Expressed in: escherichia coli. Gene: ubi1, rpl40a.
2.70Å     R-factor:   0.194     R-free:   0.247
Authors: I.Lee,H.Schindelin
Key ref:
I.Lee and H.Schindelin (2008). Structural insights into E1-catalyzed ubiquitin activation and transfer to conjugating enzymes. Cell, 134, 268-278. PubMed id: 18662542 DOI: 10.1016/j.cell.2008.05.046
23-Mar-08     Release date:   05-Aug-08    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P22515  (UBA1_YEAST) -  Ubiquitin-activating enzyme E1 1
1024 a.a.
1001 a.a.
Protein chains
Pfam   ArchSchema ?
P0CG63  (UBI4P_YEAST) -  Polyubiquitin
381 a.a.
76 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     cellular protein modification process   2 terms 
  Biochemical function     catalytic activity     6 terms  


DOI no: 10.1016/j.cell.2008.05.046 Cell 134:268-278 (2008)
PubMed id: 18662542  
Structural insights into E1-catalyzed ubiquitin activation and transfer to conjugating enzymes.
I.Lee, H.Schindelin.
Ubiquitin (Ub) and ubiquitin-like proteins (Ubls) are conjugated to their targets by specific cascades involving three classes of enzymes, E1, E2, and E3. Each E1 adenylates the C terminus of its cognate Ubl, forms a E1 approximately Ubl thioester intermediate, and ultimately generates a thioester-linked E2 approximately Ubl product. We have determined the crystal structure of yeast Uba1, revealing a modular architecture with individual domains primarily mediating these specific activities. The negatively charged C-terminal ubiquitin-fold domain (UFD) is primed for binding of E2s and recognizes their positively charged first alpha helix via electrostatic interactions. In addition, a mobile loop from the domain harboring the E1 catalytic cysteine contributes to E2 binding. Significant, experimentally observed motions in the UFD around a hinge in the linker connecting this domain to the rest of the enzyme suggest a conformation-dependent mechanism for the transthioesterification function of Uba1; however, this mechanism clearly differs from that of other E1 enzymes.
  Selected figure(s)  
Figure 2.
Figure 2. Detailed Views of the Three Uba1-Ub Interfaces
(A) Interface I involves the hydrophobic surface on Ub (yellow) and the AAD (magenta) and Phe283/Ala284 in the 4HB (pale cyan). Domains are colored as in Figure 1, including the corresponding carbon atoms, whereas nitrogen atoms are shown in blue and oxygen atoms in red. Critical residues in the interface are shown in all-bonds representation. Dashed lines indicate hydrogen bonds.
(B) Interactions between Ub's C-terminal tail (yellow) with the AAD and crossover loop (magenta) define interface II. The side chain of Arg590 of Uba1 has been omitted for clarity.
(C) Interface III is located between Ub (yellow) and the FCCH (green).
Figure 4.
Figure 4. Comparison of E1 Structures and Conformational Changes in Uba1
(A) Ribbon and surface representations of the Uba1-Ub complex (left) and the APPBP1-UBA3-NEDD8 (PDB entry 1R4M [Walden et al., 2003a]) complex (right). The catalytic cysteine is shown in pink. In the Uba1-Ub complex, the “canyon” between the SCCH and the UFD is considerably wider compared to the other complex. Arrows highlight the respective binding sites for the N-terminal helix of each E2.
(B) Conformational changes in UFD and the UFD linker observed in the Uba1-Ub crystal structure. The two copies of the Uba1-Ub complex present in the asymmetric unit were superimposed, with one complex colored in blue and the other in purple. The straight black arrow points to the UFD linker to highlight the conformational differences, whereas the curved arrow indicates the rotation of the UFD around the linker. Cys600 is highlighted as a sphere, and N and C termini of Uba1 and residues adjacent to the disordered loop in the SCCH domain are labeled.
  The above figures are reprinted by permission from Cell Press: Cell (2008, 134, 268-278) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23142976 S.E.Kaiser, K.Mao, A.M.Taherbhoy, S.Yu, J.L.Olszewski, D.M.Duda, I.Kurinov, A.Deng, T.D.Fenn, D.J.Klionsky, and B.A.Schulman (2012).
Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures.
  Nat Struct Mol Biol, 19, 1242-1249.
PDB codes: 4gsj 4gsk 4gsl
20980253 D.Y.Lin, J.Diao, D.Zhou, and J.Chen (2011).
Biochemical and structural studies of a HECT-like ubiquitin ligase from Escherichia coli O157:H7.
  J Biol Chem, 286, 441-449.
PDB codes: 3naw 3nb2
22056771 S.B.Hong, B.W.Kim, K.E.Lee, S.W.Kim, H.Jeon, J.Kim, and H.K.Song (2011).
Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8.
  Nat Struct Mol Biol, 18, 1323-1330.
PDB codes: 3rui 3ruj
21169198 T.Nunoura, Y.Takaki, J.Kakuta, S.Nishi, J.Sugahara, H.Kazama, G.J.Chee, M.Hattori, A.Kanai, H.Atomi, K.Takai, and H.Takami (2011).
Insights into the evolution of Archaea and eukaryotic protein modifier systems revealed by the genome of a novel archaeal group.
  Nucleic Acids Res, 39, 3204-3223.  
20164915 B.A.Schulman, and A.L.Haas (2010).
Structural biology: Transformative encounters.
  Nature, 463, 889-890.  
20399179 D.Völler, and H.Schindelin (2010).
And yet it moves: active site remodeling in the SUMO E1.
  Structure, 18, 419-421.  
20396627 G.Brahemi, A.M.Burger, A.D.Westwell, and A.Brancale (2010).
Homology Modelling of Human E1 Ubiquitin Activating Enzyme.
  Lett Drug Des Discov, 7, 57-62.  
20129059 J.E.Brownell, M.D.Sintchak, J.M.Gavin, H.Liao, F.J.Bruzzese, N.J.Bump, T.A.Soucy, M.A.Milhollen, X.Yang, A.L.Burkhardt, J.Ma, H.K.Loke, T.Lingaraj, D.Wu, K.B.Hamman, J.J.Spelman, C.A.Cullis, S.P.Langston, S.Vyskocil, T.B.Sells, W.D.Mallender, I.Visiers, P.Li, C.F.Claiborne, M.Rolfe, J.B.Bolen, and L.R.Dick (2010).
Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ.
  Mol Cell, 37, 102-111.
PDB code: 3gzn
20368332 J.P.Bacik, J.R.Walker, M.Ali, A.D.Schimmer, and S.Dhe-Paganon (2010).
Crystal structure of the human ubiquitin-activating enzyme 5 (UBA5) bound to ATP: mechanistic insights into a minimalistic E1 enzyme.
  J Biol Chem, 285, 20273-20280.
PDB code: 3h8v
21209884 J.Wang, A.M.Taherbhoy, H.W.Hunt, S.N.Seyedin, D.W.Miller, D.J.Miller, D.T.Huang, and B.A.Schulman (2010).
Crystal structure of UBA2(ufd)-Ubc9: insights into E1-E2 interactions in Sumo pathways.
  PLoS One, 5, e15805.
PDB codes: 3ong 3onh
19343538 M.Zheng, J.Liu, Z.Yang, X.Gu, F.Li, T.Lou, C.Ji, and Y.Mao (2010).
Expression, purification and characterization of human ubiquitin-activating enzyme, UBE1.
  Mol Biol Rep, 37, 1413-1419.  
20164921 S.K.Olsen, A.D.Capili, X.Lu, D.S.Tan, and C.D.Lima (2010).
Active site remodelling accompanies thioester bond formation in the SUMO E1.
  Nature, 463, 906-912.
PDB codes: 3kyc 3kyd
  19610673 A.M.Gulick (2009).
Conformational dynamics in the Acyl-CoA synthetases, adenylation domains of non-ribosomal peptide synthetases, and firefly luciferase.
  ACS Chem Biol, 4, 811-827.  
19352404 B.A.Schulman, and J.W.Harper (2009).
Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways.
  Nat Rev Mol Cell Biol, 10, 319-331.  
19494832 C.A.Regni, R.F.Roush, D.J.Miller, A.Nourse, C.T.Walsh, and B.A.Schulman (2009).
How the MccB bacterial ancestor of ubiquitin E1 initiates biosynthesis of the microcin C7 antibiotic.
  EMBO J, 28, 1953-1964.
PDB codes: 3h5a 3h5n 3h5r 3h9g 3h9j 3h9q
  20948667 C.Riedinger, and J.A.Endicott (2009).
All change: protein conformation and the ubiquitination reaction cascade.
  F1000 Biol Rep, 1, 0.  
19250909 D.T.Huang, O.Ayrault, H.W.Hunt, A.M.Taherbhoy, D.M.Duda, D.C.Scott, L.A.Borg, G.Neale, P.J.Murray, M.F.Roussel, and B.A.Schulman (2009).
E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification.
  Mol Cell, 33, 483-495.
PDB code: 3fn1
19675644 G.Schwarz, R.R.Mendel, and M.W.Ribbe (2009).
Molybdenum cofactors, enzymes and pathways.
  Nature, 460, 839-847.  
19443651 J.Wang, B.Lee, S.Cai, L.Fukui, W.Hu, and Y.Chen (2009).
Conformational transition associated with E1-E2 interaction in small ubiquitin-like modifications.
  J Biol Chem, 284, 20340-20348.  
19325621 M.Hochstrasser (2009).
Origin and function of ubiquitin-like proteins.
  Nature, 458, 422-429.  
19851334 Y.Ye, and M.Rape (2009).
Building ubiquitin chains: E2 enzymes at work.
  Nat Rev Mol Cell Biol, 10, 755-764.  
19602541 Y.Zhou, Z.W.Carpenter, G.Brennan, and J.R.Nambu (2009).
The unique Morgue ubiquitination protein is conserved in a diverse but restricted set of invertebrates.
  Mol Biol Evol, 26, 2245-2259.  
18802447 G.Rabut, and M.Peter (2008).
Function and regulation of protein neddylation. 'Protein modifications: beyond the usual suspects' review series.
  EMBO Rep, 9, 969-976.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.