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24361527[PMID] - PMC - NCBI

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Items: 4

1.
Figure 1

Figure 1. Structure of the antithrombin-binding pentasaccharide found in heparin. From: Heparan sulfate 3-O-sulfation: A rare modification in search of a function.

The individual residues of the pentasaccharide are numbered relative to the N-sulfo-glucosamine-3-sulfate residue at position 0. The central 3-O-sulfate group generated by Hs3st-1 (shown in red) and the 6-O-sulfate group at residue −2 (shown in blue) account for the majority of the binding energy of antithrombin to heparin. Note that the 6-O-sulfate group on the 3-O-sulfated glucosamine residue is dispensable and that residue −2 can be N-sulfated.

Bryan E. Thacker, et al. Matrix Biol. ;35:60-72.
2.
Figure 4

Figure 4. Stereo diagram of pentasaccharide-antithrombin interaction. From: Heparan sulfate 3-O-sulfation: A rare modification in search of a function.

(PDB code: 2GD4). Heparan sulfate binding residues of antithrombin (salmon) and the pentasaccharide (grey) are shown in sticks, and the antithrombin protein backbone is shown in cartoon (salmon). Putative salt bridges and hydrogen bonds stabilized by the 3- O-sulfate group and K114 are shown as broken lines. Sugar residues in the pentasaccharide are labeled as in .

Bryan E. Thacker, et al. Matrix Biol. ;35:60-72.
3.
Figure 3

Figure 3. Phylogenetic analysis of Hs3sts. From: Heparan sulfate 3-O-sulfation: A rare modification in search of a function.

The number of Hs3st isozymes identified in each species was deduced from existing publications, NCBI protein database searches and comparison of key amino acids that define substrate and catalytic sites. The phylogenetic tree depicts their evolutionary relationship (adapted from ()). The proposed origin of Hs3st is indicated with an arrow.

Bryan E. Thacker, et al. Matrix Biol. ;35:60-72.
4.
Figure 2

Figure 2. Structural interactions of 3-O-sulfotransferases with oligosaccharide substrates. From: Heparan sulfate 3-O-sulfation: A rare modification in search of a function.

(A) Stereo diagram of the interaction between Hs3st-3 and the tetrasaccharide D2S6-I2S6 (PDB code 1T8U). Side chains of critical amino acid residues that mediate substrate binding are shown as thick grey sticks. Possible hydrogen bonds between side chains and tetrasaccharide are pictured as black broken lines. The C3-OH group of the glucosamine residue to be sulfated is shown as a red sphere. The sulfate donor mimic, 3’-phosphoadenosine 5’-phosphate (PAP) is shown, and the protein backbone is shown as a cartoon in the background. (B) Superposition of Hs3st-3 bound tetrasaccharide (D2S6-I2S6; green, PDB code 1T8U) and heptasaccharide (A6-G0S6-I2S6-G0M0; white, PDB code 3UAN). The surface of Hs3st-1 is rendered in gray. Residues in tetrasaccharides are labeled as T-1 to T-4. Residues in the heptasaccharide are labeled as H-1 to H-6 (the anhydromannose residue is not shown). (C) Role of K259 in Hs3st-3 substrate recognition. The tetrasaccharide and heptasaccharide are colored and numbered as in (B). Putative hydrogen bonds between K259 and the 2-O-sulfate group of T-1 and the carboxylate of T-3 are shown in black dashed lines. The distance between the 2-O-sulfate of T-1 and carboxylate of T-3 are shown as a yellow broken line. The distance between the 2-O-sulfate of T-1 and the carboxylate of H-4 are shown as a red broken line. (D-F) Role of gate residues in substrate recognition. The gate residues are shown as large spheres and labeled in white, and the tetrasaccharide is shown with the C3-OH group shown as a red sphere. The molecular surface of each enzyme is shown in grey. The distance between gates residues is pictured as black broken lines. The tetrasaccharide is modeled into Hs3st-1 (PDB code 1VKJ) and Hs3st-5 (PDB code 3BD9) by superimposing their structures on that of the Hs3st-3/tetrasaccharide complex (PDB code 1T8U) using PyMol (Schrödinger).

Bryan E. Thacker, et al. Matrix Biol. ;35:60-72.

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