Contributor submission ArbB2

[mite-bot]

A submission was performed via the MITE web portal and needs reviewing.

Submission ID: 70007398-c22e-11f0-b219-2a1693e7738c

Review requested

@mmzdouc, @marnixmedema, @BT287, @cbeemelm, @corkdagga, @iaco-vtt

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[iaco-vtt]

The authors characterized this enzyme in vitro with a very broad variety of synthetic peptides. It seems like the enzyme needs at least a recognition sequence of at least 16 amino acid to be able to perform the cyclization reaction on the core peptide sequence of 4 or 5 amino acids. So my questions would be:

1. Should we draw the entirety of the sequences in the reaction SMARTS/SMILES, or does the core sequence (as done by submitter) suffice?
2. Should we include reactions with all (semi)natural and synthetic substrate to the known reactions? I counted at least 10 if not more

[mmzdouc]

Hey @iaco-vtt thank you for opening this issue!
Wrt your questions:

1. Yes indeed, I would definitely include the recognition sequence! If I understood correctly, the sequence KDFESKPGSFLWGYQG (ArbA2_62–77) seems to be still accepted, even if the yield is lower. In MITE, we try to display the minimum requirement for a reaction, including the precursor sequence, and this seems to be a good approximation. Therefore, the reaction of the submitter will need to be replaced.
2. Looking at the different mutants, the enzyme seems to be quite tolerant towards modifications! I think we can incorporate this in the reaction SMARTS right away, and use the sequence ALAGY for the core sequence, resulting in a precursor sequence of KDFESKPGSALAGYQG. This reaction SMARTS will then accept variable 5-aa core substrates like the wt FLWGY, but also mutants like FLILY. This way, we do not have to include all the substrates :D Even though we do not have a full analysis of all amino acids for these positions, my feeling is that the positions are indeed very variable, when we look at the aa profile of the core

Let me know if you feel comfortable changing the reaction; otherwise I am happy to take over ;)

[iaco-vtt]

Hey @iaco-vtt thank you for opening this issue! Wrt your questions:

1. Yes indeed, I would definitely include the recognition sequence! If I understood correctly, the sequence KDFESKPGSFLWGYQG (ArbA2_62–77) seems to be still accepted, even if the yield is lower. In MITE, we try to display the minimum requirement for a reaction, including the precursor sequence, and this seems to be a good approximation. Therefore, the reaction of the submitter will need to be replaced.
2. Looking at the different mutants, the enzyme seems to be quite tolerant towards modifications! I think we can incorporate this in the reaction SMARTS right away, and use the sequence ALAGY for the core sequence, resulting in a precursor sequence of KDFESKPGSALAGYQG. This reaction SMARTS will then accept variable 5-aa core substrates like the wt FLWGY, but also mutants like FLILY. This way, we do not have to include all the substrates :D Even though we do not have a full analysis of all amino acids for these positions, my feeling is that the positions are indeed very variable, when we look at the aa profile of the core

Let me know if you feel comfortable changing the reaction; otherwise I am happy to take over ;)

Hi @mmzdouc thanks for the reply, I think I can give it a shot this week :)

Just to make sure I understood correctly, for the SMARTS we can then use KDFESKPGS-ALAGY-QG, but then for the example reactions (with substrate/product pairs) we do have to show at least the others that are reported right?

[mmzdouc]

Hey @iaco-vtt no just one example is necessary! Thats the beatuy of reaction SMARTS - it represents all at once and only one example is required :)

…

On Mon, 1 Dec 2025, 08:53 Riccardo, ***@***.***> wrote: *iaco-vtt* left a comment (mite-standard/mite_data#146) <#146 (comment)> Hey @iaco-vtt <https://github.com/iaco-vtt> thank you for opening this issue! Wrt your questions: 1. Yes indeed, I would definitely include the recognition sequence! If I understood correctly, the sequence KDFESKPGSFLWGYQG (ArbA2_62–77) seems to be still accepted, even if the yield is lower. In MITE, we try to display the minimum requirement for a reaction, including the precursor sequence, and this seems to be a good approximation. Therefore, the reaction of the submitter will need to be replaced. 2. Looking at the different mutants, the enzyme seems to be quite tolerant towards modifications! I think we can incorporate this in the reaction SMARTS right away, and use the sequence ALAGY for the core sequence, resulting in a precursor sequence of KDFESKPGSALAGYQG. This reaction SMARTS will then accept variable 5-aa core substrates like the wt FLWGY, but also mutants like FLILY. This way, we do not have to include all the substrates :D Even though we do not have a full analysis of all amino acids for these positions, my feeling is that the positions are indeed very variable, when we look at the aa profile of the core [image: image] <https://private-user-images.githubusercontent.com/95709447/519871651-68392d70-833d-4296-84b0-2356c0f1fdc6.png?jwt=eyJ0eXAiOiJKV1QiLCJhbGciOiJIUzI1NiJ9.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.axpRTx_DBi-EHEwuV-oJpv6YLstlgJXlKljmKyuatVs> Let me know if you feel comfortable changing the reaction; otherwise I am happy to take over ;) Hi @mmzdouc <https://github.com/mmzdouc> thanks for the reply, I think I can give it a shot this week :) Just to make sure I understood correctly, for the SMARTS we can then use KDFESKPGS-ALAGY-QG, but then for the example reactions (with substrate/product pairs) we do have to show at least the others that are reported right? — Reply to this email directly, view it on GitHub <#146 (comment)>, or unsubscribe <https://github.com/notifications/unsubscribe-auth/AW2GSB2REJCCAX2WJCEP3LT37PXXNAVCNFSM6AAAAACMGNOVOGVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZTKOJVGA4TKMZQGU> . You are receiving this because you were mentioned.Message ID: ***@***.***>

[iaco-vtt]

Hey @iaco-vtt no just one example is necessary! Thats the beatuy of reaction SMARTS - it represents all at once and only one example is required :)
…
On Mon, 1 Dec 2025, 08:53 Riccardo, @.> wrote: iaco-vtt left a comment (mite-standard/mite_data#146) <#146 (comment)> Hey @iaco-vtt https://github.com/iaco-vtt thank you for opening this issue! Wrt your questions: 1. Yes indeed, I would definitely include the recognition sequence! If I understood correctly, the sequence KDFESKPGSFLWGYQG (ArbA2_62–77) seems to be still accepted, even if the yield is lower. In MITE, we try to display the minimum requirement for a reaction, including the precursor sequence, and this seems to be a good approximation. Therefore, the reaction of the submitter will need to be replaced. 2. Looking at the different mutants, the enzyme seems to be quite tolerant towards modifications! I think we can incorporate this in the reaction SMARTS right away, and use the sequence ALAGY for the core sequence, resulting in a precursor sequence of KDFESKPGSALAGYQG. This reaction SMARTS will then accept variable 5-aa core substrates like the wt FLWGY, but also mutants like FLILY. This way, we do not have to include all the substrates :D Even though we do not have a full analysis of all amino acids for these positions, my feeling is that the positions are indeed very variable, when we look at the aa profile of the core [image: image] https://private-user-images.githubusercontent.com/95709447/519871651-68392d70-833d-4296-84b0-2356c0f1fdc6.png?jwt=eyJ0eXAiOiJKV1QiLCJhbGciOiJIUzI1NiJ9.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.axpRTx_DBi-EHEwuV-oJpv6YLstlgJXlKljmKyuatVs Let me know if you feel comfortable changing the reaction; otherwise I am happy to take over ;) Hi @mmzdouc https://github.com/mmzdouc thanks for the reply, I think I can give it a shot this week :) Just to make sure I understood correctly, for the SMARTS we can then use KDFESKPGS-ALAGY-QG, but then for the example reactions (with substrate/product pairs) we do have to show at least the others that are reported right? — Reply to this email directly, view it on GitHub <#146 (comment)>, or unsubscribe https://github.com/notifications/unsubscribe-auth/AW2GSB2REJCCAX2WJCEP3LT37PXXNAVCNFSM6AAAAACMGNOVOGVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZTKOJVGA4TKMZQGU . You are receiving this because you were mentioned.Message ID: @.>

Alright that sounds great indeed! 😄

[mmzdouc]

70007398-c22e-11f0-b219-2a1693e7738c.json

[mmzdouc]

Merged in #152