PDBsum entry 3eay

Hydrolase

PDB id: 3eay

Contents

Protein chain

247 a.a. *

Ligands

SO4

Waters ×66

* Residue conservation analysis

PDB id:

3eay

Name:

Hydrolase

Title:

Crystal structure of the human senp7 catalytic domain

Structure:

Sentrin-specific protease 7. Chain: a. Fragment: catalytic domain: residues 662-984. Synonym: sentrin/sumo-specific protease senp7. Engineered: yes

Source:

Homo sapiens. Organism_taxid: 9606. Gene: senp7, kiaa1707, ssp2, susp2. Expressed in: escherichia coli.

Resolution:

2.40Å R-factor: 0.202 R-free: 0.256

Authors:

C.D.Lima,D.Reverter

Key ref:

C.D.Lima and D.Reverter (2008). Structure of the Human SENP7 Catalytic Domain and Poly-SUMO Deconjugation Activities for SENP6 and SENP7. J Biol Chem, 283, 32045-32055. PubMed id: 18799455 DOI: 10.1074/jbc.M805655200

Date:

26-Aug-08 Release date: 16-Sep-08

Protein chain

Q9BQF6  (SENP7_HUMAN) -  Sentrin-specific protease 7 from Homo sapiens

Seq: 1050 a.a.

Struc: 247 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.22.- - ?????

DOI no: 10.1074/jbc.M805655200

J Biol Chem 283:32045-32055 (2008)

PubMed id: 18799455

Structure of the Human SENP7 Catalytic Domain and Poly-SUMO Deconjugation Activities for SENP6 and SENP7.

C.D.Lima, D.Reverter.

ABSTRACT

Small ubiquitin-like modifier (SUMO) proteases regulate the abundance and lifetime of SUMO-conjugated substrates by antagonizing reactions catalyzed by SUMO-conjugating enzymes. Six SUMO proteases constitute the human SENP/ULP protease family (SENP1-3 and SENP5-7). SENP6 and SENP7 include the most divergent class of SUMO proteases, which also includes the yeast enzyme ULP2. We present the crystal structure of the SENP7 catalytic domain at a resolution of 2.4A. Comparison with structures of human SENP1 and SENP2 reveals unique elements that differ from previously characterized structures of SUMO-deconjugating enzymes. Biochemical assays show that SENP6 and SENP7 prefer SUMO2 or SUMO3 in deconjugation reactions with rates comparable with those catalyzed by SENP2, particularly during cleavage of di-SUMO2, di-SUMO3, and poly-SUMO chains composed of SUMO2 or SUMO3. In contrast, SENP6 and SENP7 exhibit lower rates for processing pre-SUMO1, pre-SUMO2, or pre-SUMO3 in comparison with SENP2. Structure-guided mutational analysis reveals elements unique to the SENP6 and SENP7 subclass of SENP/ULP proteases that contribute to protease function during deconjugation of poly-SUMO chains.

Selected figure(s)

Figure 3.
Structure of the catalytic domain of SENP7. A, two views of the SENP7 catalytic domain shown in ribbon representation. Secondary structure elements are either numbered (β-strands) or lettered (α-helices). The catalytic residues are depicted in stick representation near the top of each panel, and the catalytic cysteine is labeled (C926). The insertion elements (Loop-1, Loop-2, Loop-3, and Loop-4) are labeled in at least one of the two panels. Segments of the polypeptide not observed in the electron density maps were deemed disordered and are indicated by dashed lines. The N and C termini are labeled N or C, respectively. B, superposition of the SENP7 and SENP2 (PDB 1THO) structures in ribbon representation with SENP7 colored blue and SENP2 colored yellow. Catalytic residues are shown in stick representation as in A. C, superposition of SENP1 (PDB 2IYC) with SENP2 (PDB 1THO) in ribbon representation with SENP1 colored green and SENP2 colored yellow. Catalytic residues are shown in stick representation. D, alignment of sequences corresponding to the catalytic domains for human SENP7, SENP6, SENP1, SENP2, and SENP3 based on structural alignment of human SENP2 and SENP7. Gaps are denoted by dots and the large sequence insertion within Loop-3 is depicted by // to indicate that the sequence is missing from the alignment. Numbering above the sequence alignment corresponds to the amino acid position in full-length SENP7. Secondary structural elements are indicated above the alignment for SENP7 (blue) and below the alignment for SENP2 (yellow). For SENP7, β-strands are numbered, α-helices lettered, and coil depicted as a line. Missing regions in our structure are denoted by dashed lines, and the gap in Loop-3 is indicated by //. Side chain identity (75% conservation) is denoted in the alignment by a yellow background. Conserved catalytic residues are depicted in red. Graphics were prepared with PYMOL (47).

Figure 4.
Structural models for interactions between SENP7 and SUMO. A, superposition of the SENP7 and SENP2 catalytic domains in blue ribbon and yellow stick representation, respectively. The position of SUMO is indicated schematically based on the position of SUMO2 in complex with SENP2 (PDB 2IO0). Several residues within the SUMO-protease interface are highlighted in stick representation and labeled according to their position and side chain composition in SENP7. B, top panel, the structure of SUMO2-RanGAP1 (stick and transparent surface representation) is shown in complex with SENP2 (yellow ribbon representation) to indicate the position of SUMO in site A (green) and the substrate RanGAP1 in site B (pink). The bottom panel depicts the SENP7 catalytic domain in a similar orientation to SENP2 in the top panel to highlight the positions of Loop-2, Loop-3, and Loop-4 with respect to the putative SUMO interaction surfaces in site A, site B, and site C. C, close-up view of the interface between SENP2 (yellow) and SUMO2 (green) with SENP7 (blue) shown at the right in an analogous orientation to highlight residues involved in interactions with SUMO at site A. D, similar to C, but depicting the other side of the SENP2-SUMO2 complex to highlight residues in SENP7 Loop-1 that may contribute to SUMO interaction. E, electrostatic potential surface representation for SENP1, SENP2, and SENP7 to highlight similarities between SENP1 and SENP2 within the SUMO interaction surface (site A) and the differences between SENP7 and either SENP1 or SENP2 in the analogous surface. The relative position for SUMO in site A is indicated by a green circle as derived from structures of SENP1-SUMO, SENP2-SUMO and models for SENP7-SUMO.

The above figures are reprinted from an Open Access publication published by the ASBMB: J Biol Chem (2008, 283, 32045-32055) copyright 2008.

Figures were selected by the author.