PDBsum entry 2io2

Protein binding, hydrolase

PDB id: 2io2

Contents

Protein chains

225 a.a. *

75 a.a. *

156 a.a. *

Waters ×8

* Residue conservation analysis

PDB id:

2io2

Name:

Protein binding, hydrolase

Title:

Crystal structure of human senp2 in complex with rangap1-sumo-1

Structure:

Sentrin-specific protease 2. Chain: a. Fragment: catalytic domain. Synonym: sentrin/sumo-specific protease senp2, smt3-specific isopeptidase 2, smt3ip2, axam2. Engineered: yes. Mutation: yes. Small ubiquitin-related modifier 1. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: senp2, kiaa1331. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: sumo1, smt3c, smt3h3, ubl1. Gene: rangap1.

Biol. unit:

Dodecamer (from PDB file)

Resolution:

2.90Å R-factor: 0.268 R-free: 0.301

Authors:

D.Reverter,C.D.Lima

Key ref:

D.Reverter and C.D.Lima (2006). Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates. Nat Struct Mol Biol, 13, 1060-1068. PubMed id: 17099700 DOI: 10.1038/nsmb1168

Date:

09-Oct-06 Release date: 21-Nov-06

Protein chain

Q9HC62  (SENP2_HUMAN) -  Sentrin-specific protease 2 from Homo sapiens

Seq: 589 a.a.

Struc: 225 a.a.*

Protein chain

P63165  (SUMO1_HUMAN) -  Small ubiquitin-related modifier 1 from Homo sapiens

Seq: 101 a.a.

Struc: 75 a.a.

Protein chain

P46060  (RAGP1_HUMAN) -  Ran GTPase-activating protein 1 from Homo sapiens

Seq: 587 a.a.

Struc: 156 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain A: E.C.3.4.22.- - ?????

DOI no: 10.1038/nsmb1168

Nat Struct Mol Biol 13:1060-1068 (2006)

PubMed id: 17099700

Structural basis for SENP2 protease interactions with SUMO precursors and conjugated substrates.

D.Reverter, C.D.Lima.

ABSTRACT

SUMO processing and deconjugation are essential proteolytic activities for nuclear metabolism and cell-cycle progression in yeast and higher eukaryotes. To elucidate the mechanisms used during substrate lysine deconjugation, SUMO isoform processing and SUMO isoform interactions, X-ray structures were determined for a catalytically inert SENP2 protease domain in complex with conjugated RanGAP1-SUMO-1 or RanGAP1-SUMO-2, or in complex with SUMO-2 or SUMO-3 precursors. Common features within the active site include a 90 degrees kink proximal to the scissile bond that forces C-terminal amino acid residues or the lysine side chain toward a protease surface that appears optimized for lysine deconjugation. Analysis of this surface reveals SENP2 residues, particularly Met497, that mediate, and in some instances reverse, in vitro substrate specificity. Mutational analysis and biochemistry provide a mechanism for SENP2 substrate preferences that explains why SENP2 catalyzes SUMO deconjugation more efficiently than processing.

Selected figure(s)

Figure 1.
Figure 1. Structures of SENP2 deconjugation complexes with RanGAP1–SUMO-1 and RanGAP1–SUMO-2. (a) Two nearly orthogonal views of the human SENP2 catalytic domain in complex with the C-terminal domain of RanGAP1 conjugated to either SUMO-2 (left) or SUMO-1 (right), shown as ribbons. SENP2 catalytic residues are shown in bond representation, as is the isopeptide bond between lysine and the SUMO diglycine motif. (b) Stereo representation of the interaction between the SUMO-1 C-terminal tail (yellow), SENP2 (blue) and the consensus residues of RanGAP1 (magenta), with interacting residues labeled and shown in bond representation. Red dashed lines denote putative hydrogen bonds. (c) Surface representation of SENP2 in complex with the consensus residues of RanGAP1 conjugated to the SUMO-1 diglycine motif. SUMO-1 C-terminal residues (yellow) and RanGAP1 consensus motif (magenta) are shown as sticks. (d) Stereo view of Ubc9 (SUMO E2, yellow) active site in complex with RanGAP1–SUMO-1 (PDB 1Z5S)^29, depicted as in b. (e) Simulated annealing omit map contoured at 1.2 , covering the isopeptide bond and selected active site residues in the SENP2–RanGAP1–SUMO-1 structure. Graphics prepared with PyMOL^41 (http://pymol.sourceforge.net).

Figure 5.
Figure 5. Comparison of the hydrogen bond coordination of the and peptide bonds in the deconjugation and processing complexes. (a) Stick representation of isopeptide bond between RanGAP1 Lys524 and SUMO Gly97. Blue, SENP2; yellow, SUMO; magenta, RanGAP1; red dashed lines, hydrogen bonds. (b) Stick representation of scissile peptide bond between Gly92 and Val93 from pre-SUMO-3, in similar orientation as in a.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 1060-1068) copyright 2006.

Figures were selected by the author.