Table 2.
Residue Conservation: Position of Amino Acids Strictly Conserved in >70% of Sequences
| Consensus residue | % | Location | Comment |
| Phe33 | 79 | middle of hA | shutter, packs against conserved position 54 |
| Asn49 | 87 | start of s6B | gate, extensive hydrogen bond network of C-terminal residues (389–393) |
| Ser53* | 93 | end of s6B | shutter, forms hydrogen bond of backbone of conserved positions 56 and 383 |
| Pro54* | 90 | start of hB | shutter, forms tight turn |
| Ser56** | 72 | hB | shutter, makes hydrogen bond of side chain to conserved position 186 |
| Leu61 | 75 | hB | shutter, buried hydrophobic residue, packs against conserved positions 80, 184, 299, 303, and 312 |
| Gly67* | 80 | end of hB | forms tight turn, packs against conserved position 130 |
| Thr72 | 87 | start of hC | makes hydrogen bonds to loop between hI and s5A |
| Leu80 | 75 | end of hC | shutter, buried hydrophobic, packs against conserved position 61 |
| Phe130 | 75 | start of hE | packs against conserved position 67 |
| Phe147 | 84 | start of hF | packs into interface between hF and the Aβ-sheet |
| Ile157 | 83 | hF | shutter, packs into interface between hF and the Aβ-sheet |
| Asn158* | 94 | hF | shutter, forms hydrogen bonds to loop joining hF to s3A |
| Val161 | 78 | hF | shutter, packs into interface between hF and the Aβ-sheet |
| Thr165 | 89 | end of hF | shutter, inserts into Aβ-sheet in δ conformation (Gooptu et al. 2000) |
| Gly167 | 75 | end of hF | shutter, inserts into Aβ-sheet in δ conformation (Gooptu et al. 2000) |
| Ile169 | 84 | loop between hF/s3A | shutter, inserts into Aβ-sheet in δ conformation (Gooptu et al. 2000) |
| Thr180 | 75 | loop between hF/s3A | hydrogen bonding stabilizes turn into s3A |
| Leu184 | 74 | s3A | shutter, buried hydrophobic, packs against conserved position 61 |
| Asn186 | 85 | s3A | shutter, hydrogen bond to conserved position 334, Ser 56 and P8 of RCL in cleaved form (Whisstock et al. 2000a) |
| Phe190 | 95 | s3A | breach, buried hydrophobic, packs against conserved position 244 |
| Lys191 | 78 | s3A | breach, makes salt bridge to Asp 341 and hydrogen bonds to uninserted RCL |
| Gly192 | 74 | end of s3A | breach, mobile region where sheet swings open to accept RCL during loop insertion |
| Trp194 | 94 | end of s3A | breach, buried hydrophobic, packs against conserved positions 198 and 244 |
| Phe198 | 95 | s4C | breach, buried hydrophobic, packs against conserved positions 194 and 221 |
| Thr203 | 84 | s4C | gate, hydrogen bonds to conserved position 342 (Whisstock et al. 2000b) |
| Phe208 | 98 | s4C | gate, buried hydrophobic, packs against conserved positions 218, 369, and 370 |
| Val218 | 80 | s3C | gate, buried hydrophobic, packs against conserved positions 208, 220, 289, and 391 |
| Met220* | 84 | s3C | gate, buried hydrophobic, packs against conserved positions 218 and 289 |
| Met221 | 86 | s3C | breach/gate, buried hydrophobic, packs against conserved positions 289, 198, and 342 |
| Tyr244 | 76 | s2B | breach, packs against conserved positions 190 and 194. Makes hydrogen bonds to P14 of RCL in inserted form |
| Leu254 | 80 | s3B | gate, buried hydrophobic, packs against s1C and conserved position 370 |
| Pro255 | 93 | s3B | gate, buried hydrophobic, packs against conserved position 370 |
| Pro289 | 96 | start of s6A | gate, buried hydrophobic, packs against conserved positions 208, 218, 220, and 370 |
| Lys290 | 72 | start of s6A | gate, makes salt bridge to conserved position 342 |
| Leu299 | 79 | start of hI | buried hydrophobic, packs against conserved positions 61, 303, and 334 |
| Leu303 | 90 | hI | buried hydrophobic, packs against conserved positions 299 and 61 |
| Gly307 | 83 | end of hI | forms tight turn at end of hI |
| Phe312 | 90 | loop between hI/s5A | buried hydrophobic, packs underneath Aβ-sheet and against conserved position 61 |
| Ala316 | 80 | loop between hI/s5A | buried hydrophobic, packs underneath Aβ-sheet |
| Leu327 | 72 | loop between hI/s5A | buried hydrophobic, packs underneath Aβ-sheet |
| His334* | 78 | s5A | shutter, H-bond to conserved position 186 (Whisstock et al. 2000a), packs against conserved position 299 |
| Glu342* | 91 | top of s5A | breach, H-bond bond to conserved position 203, salt bridge to conserved position 290, packs against conserved position 221 |
| Gly344 | 89 | RCL | hinge region (breach when RCL inserted) |
| Ala347 | 79 | RCL | hinge region (shutter when RCL inserted) |
| Pro369* | 96 | start of s4B | gate, forms tight turn, packs against conserved position 208 |
| Phe370* | 97 | s4B | gate, buried hydrophobic packs against conserved positions 208, 254, 255, and 289 |
| Leu383* | 80 | s5B | shutter, buried hydrophobic, forms β-bulge in s5B, packs against conserved position 384 |
| Phe384 | 94 | s5B | shutter, buried hydrophobic, forms β-bulge in s5B, packs against conserved positions 190 and 383 |
| Gly386* | 89 | s5B | shutter |
| Pro391* | 95 | C terminus | gate, buried hydrophobic; packs against conserved positions 208 and 218 |
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↵α1-Antitrypsin numbering is used throughout (*) or (**) marks those conserved residues in which natural mutations have been identified that results in partial or complete dysfunction (*, for review see Stein and Carrell 1995; **, Davis et al. 1999).
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↵The interactions described in this table are based on those seen in the X-ray crystal structures of native and cleaved α1-antitrypsin.
