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[[Image:1wm2.png|left|200px|thumb|Crystal Structure of human SUMO-2 protein, [[1wm2]]]]
<StructureSection load='3kyc' size='350' scene='' caption='Human SUMO-1 (yellow) complex with SUMO-activating enzyme subunit 1 (grey),  SUMO-activating enzyme subunit 2 (green), adenosine derivative and Zn+2 ion (grey) (PDB code [[3kyc]])'>
{{STRUCTURE_1wm2|  PDB=1wm2 | SIZE=300| SCENE=SUMO/Cv/1 |right|CAPTION=Human SUMO-2 protein, [[1wm2]] }}
__TOC__
== Function ==
[[SUMO]] is a '''Small Ubiquitin-like MOdifier''' which covalently attaches to cellular proteins to modify their function.  SUMO is similar in structure but not in sequence to [[Ubiquitin|ubiquitin]].  In several organisms SUMO is called '''SMT3'''. The SUMO-conjugating enzyme (E2) is called UBC9. The sentrin specific protease (SEPN) cleaves the C-terminal peptide from SUMO which then can bind to ubiquitin activating enzyme (E1). For details on SUMO-1 protein complex see <br />
*[[Human SUMO E1 complex]] <br />
*[[Human SUMO E1 complex with a SUMO1-AMP mimic]]<br />
*[[Human SUMO E1~SUMO1-AMP tetrahedral intermediate mimic]].


[[SUMO]] is a small ubiquitin-like modifier which covalently attaches to cellular proteins to modify their function.  SUMO is similar in structure but not in sequence to ubiquitin.  In several organisms SUMO is called SMT3.  The SUMO-conjugating enzyme is called UBC9.  The sentrin specific protease (SEPN) cleaves the C-terminal peptide from SUMO which then can bind to E1. The images at the left and at the right correspond to one representative SUMO, ''i.e.'' the crystal structure of human SUMO-2 protein ([[1wm2]]).
== Relevance ==
Sumoylation may have a potential role in Alzheimer disease and decrease sumoylation of lamina A is a causative factor in familial dilated cardiomyopathy<ref>PMID:19282183</ref>.


{{TOC limit|limit=2}}
== Structural highlights ==
[[Ubiquitin]] (Ub) and ubiquitin-like (Ubl) proteins attached to their target proteins and modulating the activities of those targets in various ways. Three types of evolutionarily conserved enzymes — E1 activating enzymes, E2 conjugating enzymes and E3 ligase enzymes — act sequentially through parallel yet distinct pathways to conjugate ubiquitin and Ubl proteins, such as SUMO and NEDD8, to their targets. The E1 enzyme uses the <scene name='3kyc/Cv/3'>adenosine triphosphate (ATP)</scene> and magnesium to adenylate the C-terminal Ub/Ubl glycine, releasing pyrophosphate and resulting in <scene name='3kyc/Cv/8'>adenosine monophosphate (AMP)</scene>. A non-hydrolysable <scene name='3kyc/Cv/4'>mimic of the acyl adenylate intermediate (AMSN)</scene> and <scene name='3kyc/Cv/5'>mimic of the tetrahedral intermediate (AVSN)</scene> were constructed. In both these compounds the atom of <font color='orange'><b>phosphorus</b></font> is replaced by sulfur (colored <font color='yellow'><b>yellow</b></font>).


== 3D Structures of SUMO ==


The <scene name='3kyc/Al/2'>structural alignment</scene> of the crystal structures for human SUMO E1 in complex with SUMO adenylate (AMSN) and tetrahedral intermediate (AVSN) analogues revealed opened conformation (<font color='orange'><b>SUMO1 in orange</b></font>, <font color='blue'><b>SAE1 colored in blue</b></font>, and <font color='darkviolet'><b>other domains in darkviolet</b></font>) and closed conformation (<font color='yellow'><b>SUMO1 in yellow</b></font>, <font color='cyan'><b>SAE1 colored in cyan</b></font>, and <font color='magenta'><b>other domains in magenta</b></font>), respectively. In the <scene name='3kyc/Al/7'>open conformation</scene> ([[3kyc]]) the distance between Cys domain (including Cys173) and mimic of the acyl adenylate intermediate AMSN is very long, while in the <scene name='3kyc/Al/6'>closed conformation</scene> ([[3kyd]]), the catalytic Cys173 is posioned near AVSN and SUMO1, so the overall structure revealed dramatic rearrangement. This large conformational change forms the <scene name='3kyc/Al/8'>E1~SUMO1-AVSN tetrahedral intermediate analogue</scene>.<ref>PMID:20164921</ref>


=== SUMO ===
[[Image:Kyc_smaller.gif|275px|left|thumb]]
<br>
<br>
For better understanding of the difference between these two conformations you can see this [[Morphs|morph]] (generated by using [http://polyview.cchmc.org/polyview3d.html POLYVIEW-3D: http://polyview.cchmc.org/polyview3d.html]; reload/refresh this page to restart this movie). Of note, in contrast to the previous figure, the same domains of these two structures ([[3kyc]] and [[3kyd]]) are colored in the same colors (<font color='yellow'><b>SUMO1 in yellow</b></font>, <font color='blue'><b>SAE1 colored in blue</b></font> and <font color='darkviolet'><b>other domains in darkviolet</b></font>). The catalytic Cys173 is shown in the spacefill representation and colored green, AMSN (or AVSN) are shown in the spacefill representation and colored in CPK colors.


== 3D Structures of SUMO ==
[[SUMO 3D Structures]]


[[2k8h]] – SUMO – NMR – ''Trypanosoma brucei''<br />
</StructureSection>
[[1u4a]] – hSUMO-3 (mutant) – NMR – human<br />
{{Clear}}
[[1wm2]], [[1wm3]] – hSUMO-2<br />
 
 
=== SUMO+ubiquitin-like SUMO-conjugating enzyme ===
 
 
[[2vrr]], [[2uyz]] – mSUMO-1+UBC9<br />
[[2pe6]] - hSUMO-1+UBC9<br />
 
 
 
=== SUMO+sentrin specific protease ===
 
 
[[2io0]] – pre-hSUMO-2+SEPN2<br />
[[2io1]] - pre-hSUMO-3+SEPN2<br />
[[2g4d]] - hSUMO-1+SEPN1<br />
[[2iy1]] - hSUMO-1+SEPN1 (mutant)<br />
[[2iyd]], [[2ckh]] - hSUMO-2+SEPN1<br />
[[1tgz]] - hSUMO-1+SEPN2<br />
[[2io3]] - pre-hSUMO-2+SEPN2 (mutant)+RAN GTPase-activating enzyme (mutant)<br />
[[2iy0]] - hSUMO-1+SEPN1 (mutant)+RAN GTPase-activating enzyme <br />
 
 
=== SUMO+other proteins ===
 
 
[[2asq]] – hSUMO-1+SUMO-binding motif in PIASX<br />
[[3kyc]], [[3kyd]] – hSUMO+SUMO-activating enzyme <br />
[[2rpq]] – hSUMO-3+activating transcription factor <br />
 
 
=== SUMO+ubiquitin-conjugating enzyme ===
 
 
[[1z5s]] - hSUMO-1+E2+ RAN GTPase-activating enzyme<br />
[[2bf8]] - SUMO-1+E2 - bovine<br />
 


=== SMT3 ===
==Reference==
<references/>




[[2k1f]] – SMT3 – Fruit fly<br />
[[Category:Topic Page]]
[[2eke]] – ySMT3+UBC9 – yeast<br />
[[1euv]] – ySMT3+ULP1 protease<br />
Retrieved from "https://proteopedia.org/SUMO"