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An Exploration of the Carbohydrate Universe

An Exploration of the Carbohydrate Universe. Amanda Ullmer Mahd Nishtar. Overview. Internship goal: Identify saccharides in the chemical component dictionary Develop queries capable of detecting saccharides Confirm query results by comparing to Kim’s list

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An Exploration of the Carbohydrate Universe

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  1. An Exploration of the Carbohydrate Universe Amanda Ullmer Mahd Nishtar

  2. Overview • Internship goal: • Identify saccharides in the chemical component dictionary • Develop queries capable of detecting saccharides • Confirm query results by comparing to Kim’s list • Classify sugars in context of remediation • C5 and C6 rings and open chain saccharides • Analyze context of saccharides within PDB structures • Link record analysis

  3. 1557 9494 Key Green: Ligands Red: Instances Ring Saccharides Open Chain Saccharides 20 2358 13 46 4 4 87 437 897 6994 125 525 478 5613 63 296 174 1051 795 6275 1134 7510 9 15 188 1005

  4. Query-Kim List Comparison • Final Results • Final Query List: • 1557 ligands • 9494 instances • Kim’s List: • 861 ligands • 7270 instances • *Query covers 100% of Kim’s list of saccharides and identifies 696 additional ligands. DNA Linking Saccharide but in polymer Key White: additional sugars Pink: common sugars Yellow: not sugars

  5. All Removed Structures from KH List, Accompanying Explanation

  6. Ligand and Structure Breakdown 216 Ligands 966 Structures 911 Ligands 7,207 Structures 72 Ligands 311 Structures 3-Carbon and 4-Carbon 7-Carbon and More 5-Carbon and 6-Carbon Saccharides Open-Chains: 174 Ligands 1,051 PDB IDs Open-Chains: 208 Ligands 957 PDB IDs Open-Chains: 9 Ligands 15 PDB IDs Rings: 63 Ligands 296 PDB IDs Rings: 8 Ligands 9 PDB IDs Rings: 737 Ligands 6,156 PDB IDs

  7. RINGS 5-Carbon and 6-Carbon Saccharides 7-Carbon and More 4-Carbon 1RB AMU 18D CC5 D5G GPO CBN 7CA

  8. OPEN-CHAINS 5-Carbon and 6-Carbon Saccharides 7-Carbon and More 3 and 4-Carbon 2FP 3A1 DLZ DSK 6PG LFC CBA WQP

  9. Initial Link Analysis

  10. Gathering and Output of Data

  11. Carbohydrate Context Overview (5,6-C) Total Exclusively Free-Floating Contains Linked Sugar Exclusively Free-Floating Oligo Exclusively Monosaccharide Glycosylation Exclusively Oligosaccharide Glycosylation Mixed: May Contain Linked Oligos (Sug-sug + sug-aa), Free-floating Oligos (Sug-sug), Linked Monosaccharides Sugar-Other Linkage

  12. Seqres Overview Total Must Contain Sugar-Sugar Must Contain Sugar-Other Must Contain Sugar-Amino Acid Or any combination thereof

  13. Sugar-antibiotic, inhibitor, etc. Exclusively Oligosaccharide Glycosylation Exclusively Free-Floating Oligosaccharide Exclusively Monosaccharide Glycosylation Exclusively Free-Floating Protein Protein,DNA,RNA Protein Protein Protein 193 PDB IDs 3,019 PDB IDs 899 PDB IDs 946 PDB IDs 1,273 PDB IDs Includes Antibiotics: 50 PDB IDs Add Free-Floating Saccharide Ligands  Protein,DNA,RNA Protein Protein Protein 221 PDB IDs 1,067 PDB IDs 1,613 PDB IDs 1,090 PDB IDs Includes Antibiotics: 53 PDB IDs

  14. Exclusively Free-Floating Oligosaccharide Sugar-antibiotic, inhibitor, etc. Exclusively Monosaccharide Glycosylation Exclusively Free-Floating Exclusively Oligosaccharide Glycosylation Condition: Condition: Condition: Condition: Condition: >At least 1 #Sugar-sugar >At least 1 #Sugar-protein >#Sugars with links = #Sugar-Sugar + #Sugar-protein >No struct_conn link record >0 #Free-floating sugars >0 free-floating >At least 1 #Sugar-other >May include other linkage >0 #Sugar-protein >At least 1 #Sugar-sugar >#Sugars with links = (#Sugar-sugar) + 1,2,3.. >0 #Sugar-sugar > At least 1 #Sugar-protein ># Sugars with links = #Sugar-protein For structures that exclude free-floating monosaccharides: #Sugars = Sugars with links For structures that additionally include free-floating monosaccharides: #Sugars > #Sugars with links

  15. Sugar-antibiotic, inhibitor, etc. Exclusively Oligosaccharide Glycosylation Exclusively Free-Floating Oligosaccharide Exclusively Monosaccharide Glycosylation Exclusively Free-Floating Example Structures: Example Structures (No FF Ligands): Example Structures (No FF Ligands): Example Structures (No FF Ligands): Example Structures (No FF Ligands): 1L6L 4FBY 3ARC 3LW5 3QAZ 1GO6 2XAD 3RUL 1QJQ 1BP8 1Q55 1Q5B 1Q5A 2QAD 3IDY 1W8H 3OFL 1FBH 1ZHS 1JPC 2QC1 1DP5 1FC2 1GYA 1HD4 Example Structures (w/ FF Ligands): Example Structures (w/ FF Ligands): Example Structures (w/ FF Ligands): Example Structures (w/ FF Ligands): 2W5U 2C5C 1FDJ 1MD2 1E72 3THC 3THD 3I1L 1HGY 2NY1 1DPJ 1G0V 2VOL 1AXD 1HWM 2C5C 1BOS 1VBO 1V6V 2D3N

  16. Mixed Cases Free-Floating Oligosaccharides Monosaccharide Glycosylation Protein Oligosaccharide Glycosylation Free-Floating Monosaccharides All: 294 PDB IDs 3TGX 2WR1 3IYU 1JS8 3O97 No FF: 229 PDB IDs 2DF3 1G9F 2WNE 3ZYR 2W52

  17. Oligosaccharide Ligands and PDB IDs All Seqres Structures 32 PDB IDs 1C58 3IRL 3IRK 3IRJ 3IRI 1AGA 1CAP 1CAR 2HYA 3HYA Chemical Class: Oligosaccharides 188 Ligands 1,005 PDB IDs 1A0T 1A7L 1AFC 1AGM 1AHP 1AZX 1B9Z 1BB5 1BB6 1BB7 1BYD

  18. Free-Floating Ligands NAG NAG MAL 3D2U with free ringed monosaccharide NAG 2QTS with free oligosaccharide ligand INI Additional Examples of Free-Floating Ligands: BOG, GAL, CAP, DGD, BGC, 2CV, KAN

  19. Free-Floating and Linked Ligands NAG NAG NAG SIA MAN 2HRR: Free-floating O-Sialic Acid and N-acetyl glucosamine linked to ASN MAN 3GXP: Free-floating Mannoses and linked NAG-NAG-ASN

  20. Monosaccharide Glycosylation NAG 4FAO NAG 3KBP

  21. Oligosaccharide Glycosylation 2QC1

  22. Free-Floating Oligosaccharides BGC FUC FUC GAL A2G 2O2L: Enterotoxin in complex with a blood group A antigen analog

  23. Sugar-Other (non-sugar, non-amino acid) Linkages Contains Antibiotics DDL DXA OMY DVC MG DRI DDA 1HHY: Sugar Ligand DVA – OMY in Deglucobalhimycin in complex with D-Ala-D-Ala 1CP8: NMR STRUCTURE OF DNA COMPLEXED WITH NOVEL ANTITUMOR DRUG UCH9

  24. Sugar-Other (non-sugar, non-amino acid) Linkages Other Structures CRYSTAL STRUCTURE OF THE SORGHUM BICOLOR DHURRINASE 1 CHOLERA TOXIN B-PENTAMER 1LLR 1V03 BGC FNG LNQ IPH

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