text:
Kaas Q et al. (2012) Nucleic Acids Res.
Search a Protein Nucleic acids 3D structure name
About ConoServer
About conopeptides
Search a peptide
Search a nucleic acid
Search a 3D structure
Search by peptide mass
Search by sequence stretches
Search by references
ConoPrec: precursor analysis
ConoMass 1: differential PTM masses
ConoMass 2: identify peptide mass
Compare mass lists
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On classification schemes
On superfamily signal sequences
On cone snail species
On 3D structures
On structural scaffold conservation
On journals in ConoServer
Gene superfamilies
Cysteine frameworks
Pharmacological families
About conotoxins
Conotoxin name scheme
Targets of conotoxins
Post translational modifications of conotoxins and conopeptides
Recent key review articles
Conotoxins feature a vast array of post translational modifications (PTMs). PTMs are chemical or structural changes to the residues of a peptide that are not encoded in the peptide gene. PTMs are introduced by specialized enzymes that change the nature of a specific residue. It is believed that the enzymes involved identify their targets by their signal and/or propeptide sequence.
The PTM best understood is the processing of the prepropeptide, which is encoded by the gene, into the mature conopeptide. In this process the N-terminal signal sequence and N-terminal and C-terminal propetides are cleaved to yield the mature peptide with their disulfide connectivity. Cleavage of C-terminal residues may result in an amidated C-terminus, often found in conotoxins. Cleavage of the N-termini of glutamine may result in the formation of pyroglutamic acid by formation of a cyclic amide from the glutamic acid side chain and N-terminus. Other chemical modifications like bromination, hydroxylation, γ-carboxylation or sulfation have also been discovered in conopeptides.
Post translational chemical modifications of amino acids found in conopeptides. 1: pyroglutamic acid (N-terminal, e.g Contulakin-G), 2: C-terminal amidation (often found on the last cysteine, e.g.SI), 3: γ-glutamic acid (e.g Conantokin-G), 4: 4-hydroxyproline (e.g MrIA), 5: sulfotyrosine (e.g EpI) and 6: 6-bromotryptophan (e.g GVIIIA).
Besides the introduction of small functional groups into an amino acid, PTMs can also introduce large molecules like carbohydrates to the side chain of an amino acid (glycosylation). Additionally, the stereo chemistry of amino acids can be changed yielding D-amino acids instead of the L-amino acid.
Post translational chemical modifications of amino acids found in conopeptides. 7: O-glycosylation of threonine (e.g Contulakin-G), 8: epimerized and chemically modified D-γ-hydroxy-valine (e.g.mus-V) and 9: D-phenyl alanine (e.g r11a)
PTM name
# conopeptides
Wild type
[2-mercaptoethyl]trimethylammonium (thiocholine) cysteine 1 (1) 0 1
Tetrahydroisoquinoline-1-carboxylic acid 1 (1) 0 1
Tert-Butyl Glycine 1 (1) 0 1
Sulfotyrosine 24 (23) 6 17
Serine 1 (1) 0 1
Selenocystine (half) 11 (11) 0 11
Selenocysteine 30 (30) 0 30
S-methylthio cysteine 1 (1) 0 1
S-cysteinylated cysteine 2 (2) 1 1
Pyroglutamic acid 135 (122) 22 100
Phenylalanine 1 (1) 0 1
Penicillamine [oxidised] 1 (1) 0 1
Oxomethionine 6 (6) 5 1
Ornithine 2 (2) 0 2
O-methyl-tyrosine 4 (4) 0 4
Norleucine 13 (13) 0 13
Norarginine 3 (3) 0 3
Napthylalanine 1 (1) 0 1
Naphthyl-2-carboxyl proline 2 (2) 0 2
N-term benzoyl 6 (6) 0 6
N-term 4-fluorobenzyl 1 (1) 0 1
N-term 4-fluorobenzoyl 1 (1) 0 1
N-term 4-chlorobenzyl 2 (2) 0 2
N-term 3-chlorobenzoyl 1 (1) 0 1
N-term 3-bromobenzyl 1 (1) 0 1
N-term 3-bromobenzoyl 1 (1) 0 1
N-methyl valine 1 (1) 0 1
N-methyl glycine 2 (2) 0 2
N-methyl (half) cystine 1 (1) 0 1
N-Acetate (on N-terminus) 5 (5) 0 5
Methanimine 2 (2) 0 2
Mercaptoethylglycine [oxidised] 2 (2) 0 2
Lysine 1 (1) 0 1
L-Penicillamine 1 (1) 0 1
L-β-amino-alanine 1 (1) 0 1
L-β,β-diphenylalanine 1 (1) 0 1
L-homophenylalanine 1 (1) 0 1
L-homolysine 2 (2) 0 2
L-4,5-dithiolnorvaline 1 (1) 0 1
L-3-pyridylalanine 1 (1) 0 1
L-3-benzothienylalanine 1 (1) 0 1
L-2-thienylalanine 1 (1) 0 1
L-2-furylalanine 1 (1) 0 1
L-2,4-diaminobutyric acid 4 (4) 0 4
L-2,3-diaminopropionic acid 2 (2) 0 2
β-homolysine 1 (1) 0 1
Homoleucine 1 (1) 0 1
Homocysteine 3 (3) 0 3
Homoarginine 3 (3) 0 3
glycosylated threonine 5 (3) 3 0
glycosylated serine 5 (2) 2 0
Glycine 2 (2) 1 1
Glutathionylated cysteine 1 (1) 0 1
Glutamic acid 1 (1) 0 1
gamma-hydroxy-D-valine 2 (2) 2 0
Gamma carboxylic glutamic acid 131 (106) 72 34
Dimethyllysine 2 (2) 0 2
Diiodotyrosine 1 (1) 0 1
D-tyrosine 3 (3) 0 3
D-tryptophan 43 (39) 18 21
D-serine 2 (2) 0 2
D-proline 1 (1) 0 1
D-phenylalanine 11 (8) 5 3
D-methionine 2 (0) 0 0
D-lysine 2 (2) 0 2
D-leucine 11 (4) 4 0
D-histidine 1 (1) 0 1
D-cysteine 10 (10) 0 10
D-aspartic acid 2 (2) 0 2
D-asparagine 1 (1) 0 1
D-arginine 60 (60) 0 60
D-alanine 2 (2) 0 2
Cystine (half) 1 (1) 0 1
Cyclohexylalanine 55 (55) 0 55
cyclohexaglycine 2 (2) 0 2
Citrulline 9 (9) 1 8
carboxyl-phenylalanine 1 (1) 0 1
Carbabridge [C7 unsaturated] (half) 1 (1) 0 1
Carbabridge [C4 saturated] (half) 1 (1) 0 1
C-term amidation 1184 (1016) 230 786
Bromotryptophan 24 (22) 22 0
Benzoylphenylalanine 2 (2) 0 2
Benzoyl proline 20 (20) 0 20
Asymmetric dimethylarginine 2 (2) 0 2
Aspartic acid 1 (1) 0 1
Asparagine 1 (1) 0 1
Arginine 1 (1) 0 1
alpha-aminosuberic acid 3 (3) 0 3
alpha-aminopimelic acid 7 (7) 0 7
alpha-aminobutyric acid 2 (2) 0 2
alpha-aminoadipic acid 3 (3) 0 3
Alanine 1 (1) 0 1
5-hydroxy-lysine 2 (1) 1 0
5-amino-3-oxo-pentanoic acid 1 (1) 0 1
5-(R)-phenyl-proline 2 (2) 0 2
4-nitrous-benzyl proline 1 (1) 0 1
4-Methyloxide-benzyl proline 1 (1) 0 1
4-mercaptoproline [reduced] 2 (2) 0 2
4-Hydroxyproline 519 (454) 146 308
4-hydroxybenzyl proline 1 (1) 0 1
4-fluoro-phenylalanine 1 (1) 0 1
4-chloro-phenylacetyl 1 (1) 0 1
4-(S)-phenyl-proline 2 (2) 0 2
4-(S)-fluoro-proline 2 (2) 0 2
4-(S)-amino-proline 2 (2) 0 2
4-(R)-guanidino-proline 2 (2) 0 2
4-(R)-fluoro-proline 2 (2) 0 2
4-(R)-betainamidyl-proline 2 (2) 0 2
4-(R)-benzyl-proline 2 (2) 0 2
4-(R)-amino-proline 2 (2) 0 2
4-(R)-1-naphtylmehyl-proline 2 (2) 0 2
3S-3-amino-1-carboxylmethylcaprolactam 1 (1) 0 1
3-quinoline carboxylic acid 1 (1) 0 1
3-iodotyrosine 3 (3) 0 3
3-aminonapthylaline-2-carboxylic acid 1 (1) 0 1
3,4-chlorobenzyl proline 1 (1) 0 1
2-mercaptoethanesulfonate-cysteine 1 (1) 0 1
2-aminoethanethiol (cysteamine) cysteine 21 (21) 0 21
2-aminobenzoyl 1 (1) 0 1
2-amino-DL-dodecanoic acid 2 (2) 0 2
2,2-dimethylthiazolidine 1 (1) 0 1
1-naphtyl-alanine 2 (2) 0 2
1,2,3,4-l-tetrahydroisoquinoline-3-carboxylic acid 3 (3) 0 3
Conopeptide amino acid post-translational modifications (PTMs) and corresponding number of conopeptides in ConoServer. The second column indicates the number of conopeptides in ConoServer for each PTM, and the numbers between parentheses indicate the numbers of synthetic and wild type conopeptides with experimental evidence of the PTM. Therefore the difference between the two numbers in the second column is the number of conopeptides for which the PTM was predicted in wild type conopeptides. The third column indicates the number of wild type conopeptides with experimental evidence of each PTM. The fourth column indicates the number of synthetic conopeptides synthesized with a PTM. Therefore the numbers between parentheses in the second column are the sum of the corresponding numbers in the third and fourth columns. Clicking on the numbers in violet gives access to the list of corresponding conopeptides.
Remark: There are presently no experimental evidence of the occurrence of D-methionine in conopeptides. Two sequences of conopeptides predicted from mRNA have been suggested to contain D-methionine because of a strong homology in a series of D-amino acid containing conopeptides.
Please cite:
Kaas Q, Yu R, Jin AH, Dutertre S and Craik DJ. ConoServer: updated content, knowledge, and discovery tools in the conopeptide database. Nucleic Acids Research (2012) 40(Database issue):D325-30
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6
ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia.
The database and computational tools found on this website may be used for academic research only, provided that it is referred to ConoServer, the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David Craik (d.craik@imb.uq.edu.au).


Unique identification guide is effective, filled with color photos, and easy to use in winter, spring, summer, and fall. Field-tested by forestry experts.
Michael D. Williams worked as an area forester with the Tennessee Division of Forestry. He was widely known for his uncanny ability to explain complicated forestry concepts in terms that were fresh, simple, and practical enough for even novices to understand.


MK Avi Dichter calls on Supreme Court to reject petition by Arab NGO Adalah to return bodies of terrorists killed in terror tunnel.
MK Avi Dichter (Likud), chairman of the Knesset Foreign Affairs and Defense Committee, said Sunday Israel's Supreme Court must reject a petition demanding a Hamas rescue team be allowed to enter to try to save terroristx. It was later announced that all the terrorists killed in the blast when the IDF destroyed a terror tunnel leading from the Gaza Strip into Israeli sovereign territory.
A total of 12 terrorists, most of them members of the Islamic Jihad terrorist organization, have been held by the IDF since a controlled explosion, using new and undisclosed technology, destroyed the terror tunnel.
The organization then withdrew its first petiition, but sided witht the terrorist families demand for return of their bodies, claiming: "The holding of bodies contradicts the principles of international humanitarian law. Bodies of individuals who are killed during situations of conflict must be returned to their families for burial with dignity. international humanitarian law prohibits using bodies for political purposes or as bargaining chips."
"The bodies of the terrorists who were taken out of the tunnel by the IDF are a bargaining chip in the negotiations over our soldiers and our citizens in the hands of Hamas," Dichter said.
Dichter said there was no reason to return the bodies at this stage. "Until they bring our sons home, the bodies of the terrorists should not be released."
"The Supreme Court must reject outright the demand of the hypocrites who are hiding behind the name of the Justice Organization - known in Arabic as Adalah."
A spokesperson for Adalah reached out to Arutz Sheva to dispute MK Dichter's claim that Adalah had filed a separate petition to Israel's Supreme Court regarding the return of the terrorists' remains.
"The statements made by Knesset Member Avi Dichter are entirely unfounded. Adalah has not filed a Supreme Court petition demanding that the state return the bodies of five deceased Palestinians to Gaza."


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I play golf around 40 times a year at multiple course around Ft. Worth and Denton. This course is the worst I have ever played at. There is a park that runs parallel to the course and when I was teeing off a man was smoking weed next to us at the park. They also had 0 carts coming around with drinks and food. And then after my round I found that my car had been broken into. I was parked right next to the clubhouse and my car was visible from the desk. I went in to tell the person at the desk and he said there was nothing he could do. They had security cameras and he told me that we couldnt look at them. Safe to say that I will never golf there again.


76 West Warehouses, LLC. filed as a Florida Limited Liability in the State of Florida on Tuesday, February 14, 2012 and is approximately seven years old, according to public records filed with Florida Department of State.
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text:
Q: Unable to insert record into join/lookup/link table (EF/FluentAPI/MVC) Alright so I'm a bit stuck at the moment.  We've creating an MVC application using EF, fluent api, etc. and I'm having some trouble getting new records into a join table at the moment.
DB Table structure
User
(pk)ID
Username
passwordhash
etc.
etc.
DDRRole
(pk)ID
(fk)RoleId
(fk)DDRId
UserRole
(pk,fk)UserId
(pk,fk)DDRRoleId
Role
(pk)ID
Name
DDR
(pk)ID
Name
class structure
the classes for the tables are what you'd expect having the props for the columns and for example User has anICollection<DDRRole> DDRRole and DDRRole has an ICollection<User> User
Here's the fluent api part (not all of it, but the part that deals with the join table):
modelBuilder.Entity<User>()
            .HasMany(uc => uc.DDRRole)
            .WithMany(dd => dd.User)
            .Map(x =>
                {
                   x.MapLeftKey("UserID");
                   x.MapRightKey("DDRRoleID");
                   x.ToTable("UserRole");
                });

so what's going wrong is when we're creating a new user that part is fine, but as we're creating the new user we want to give that user a DDRRole (which is already in database), which will then get added to the UserRole table.  I've searched a ton on this with what to do supposedly with fluent api and other things but haven't gotten this to work yet.
thanks in advance for the help

A: Ok so I figured out what was going on (kind of)....so inside my create method I was passing my User object that just got created to the method that was trying to add the role and something with that wasn't working well with each other.....long story short I passed in the new user's id and then did a db.find(userid) into a new object and there added the role to that....upon savechanges() the insert worked.

redpajama_set_name: RedPajamaStackExchange


The screen is definitely replaceable. The only thing though is that the screens are very expensive, costing upwards of $300 sometimes, depending on the quality. The "iPhone is Disabled" message usually happens when the phone's internal clock resets due to an extremely discharged battery, though it could be a different cause, and can be fixed by connecting to iTunes and restoring it by going into restore or DFU mode. As for the phone not ringing out or charging, that seems like a problem with the speakers and lightning port. Overall, this phone seems to be very abused, and likely will be very costly to repair. You could take it to Apple and see if you can get it repaired or replaced, or you can go Third-Party, and although it will likely be cheaper, the parts might not be the best quality. Since the phone is new, I would recommend going to Apple instead. Next time, though, get a case and screen protector. Rhinoshield makes great quality screen protectors and cases.
Screen is repairable but usually more expensive than previous models. I recommend Apple due to the fact that you can retain your warranty and the phone is still quite new.
Iphones with broken screens usually go into disabled mode when the touch function is triggering itself due to the damage and it inputs the passcode wrong too many times. You can recover through itunes but you may have lost your data if it isn't backed up.
I totally agree with Beninja, due to the fact that this phone is quite new I would at least try and take it into the Apple Store; and at least see what the people there have to say. It never hurts to try.
Unfortunately, DIY doesn't look like an option quite yet for this phone as I cannot find a screen replacement part from a known-trustworthy source, yet. Later on down the road that will for sure be an option.
There will be some disassembled screens on the market, these screens are of good quality, but the price is very expensive.


The Division 2's First Raid, Operation Dark Hours, Gets a Confirmed Release Date for Later This Month; New Specialization "Coming Soon"
Tom Clancy's The Division 2 is getting its first set of major updates for the month of April known as Invasion: Battle for D.C. It will include the addition of the game's first eight person raid activity, Operation Dark Hours, along with a host of other new content.
Let's start with the raid. Operation Dark Hours will release on April 25. The trailer for the updates (see below) is still light on specific details however. It reiterates what we know already, that this will be an activity that you will need to "gear up" for as it will put you your teammates' skills to the test.
Dropping sooner than that is the game's next Stronghold, Tidal Basin, which is advertised as the most heavily defended and dangerous one to-date. The Tidal Basin Stronghold will release tomorrow, April 5, and will also include two new exotic weapons: The Pestilence Light Machine Gun, and the Nemesis Sniper Rifle.
On top of that, there will be new gear sets (Hard Wired, Ongoing Directive, & True Patriot), a new PvP map called Fort McNair, and an apparel event which will encourage players to show off their style. Once again, this all will drop at some point tomorrow, and is free to all Division 2 players.
Finally, the trailer also teases a new specialization although a firm release date was not yet provided. It's just listed as "Coming Soon" for now. It is confirmed that it will have its own signature weapon.
If you're interested in tackling the first raid, hopefully the new content dropping tomorrow will help put you over the top in surviving what will likely be the toughest challenge in The Division 2 for quite a bit of time when it releases on April 25.
If you're still on the fence on whether or not to pick up The Division 2, check out our scored review, or compare it to some of the other popular looter-shooters on the market.


Chris Van Strander and David Koteles'Edison's Elephant plays The Metropolitan Playhouse Jan. 16-25.
Presented by The Metropolitan Playhouse and Joe Trentacosta, the limited engagement is part of the Metropolitan Playhouse Gilded Age Festival.
David Elliott directs a cast that includes Lynn Berg, Kevin Orton, Alyssa Simon, CJ Trentacosta, Wendy Merritt, John Thomas Waite and Rik Walter with Sean Gough on piano.