The pacifastin inhibitor family web site
[Introduction] [Sequences] [Alignments] [Structures] [Phylogenetics] [References]
Created and maintained by Zoltán Gáspári
E-mail: szpari@para.chem.elte.hu
Last modified: 24.04.2003
Structures
The fold of the inhibitors comprises three antiparalel β-strands with three disulfide bridges. The protease binding loop is located near the C-terminus and is flanked by two of the disulfides.
Figures in this page were prepared with RasMol.
Gallery
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| NMR Strcucture of SGCI (PDB code 1KGM, model 5). The position of Phe10 is indicated | NMR Strcucture of SGTI (PDB code 1KJ0, model 6). The position of Lys10 and Trp25 is indicated |
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| Crystal structure of PMP-C complexed with chymotrypsin (PDB code 1GL1). | Crystal structure of PMP-D2 complexed with chymotrypsin (PDB code 1GL0). |
Available structures
Structures are available from the PDB web site www.rcsb.org
| Inhibitor | Description | PDB |
| PMP-C | NMR, 36 structures | 1PMC |
| PMP-C | Complex with chymotrypsin | 1GL1 |
| PMP-D2 Arg29Leu, Lys30Met | Complex with chymotrypsin | 1GL0 |
| SGCI | NMR, 10 structures | 1KGM |
| SGCI Leu30Arg, Lys31Met | NMR, 10 structures | 1KIO |
| SGTI | NMR, 10 structures | 1KJ0 |
See also the corresponding SCOP family denoted PMP inhibitors
Structurally related proteins
The fold characteristic of the pacifastin family does not fulfill the criteria established for 'cystine knots' (Craik,J.D., Daly,N.L. amd Waine,C. (2001) The cystine knot motif in toxins and implications for drug design. Toxicon 39, 43-60.)
The disulfide pattern (abcacb) characteristic of the family was not found in other 'all-beta' peptides in the PDB (Release 102). The PDB was searched using a perl script converting the 'SSBOND' records into the pattern used in Carugo,O., Lu,S., Luo,J, Gu,X., Liang,S., Strobl,S. and Pongor,S. (2001): Structural analysis of the amaranth alpha-amylase inhibitor: classification within the knottin fold superfamily and analysis of its functional flexibility. Protein Eng. 14 629-637.
Structurally related proteins were identified using an in-house program using the principles of the PRIDE method (Carugo & Pongor (2002): Protein fold similarity estimated by a probabilistic approach based on C(alpha)-C(alpha) distance comparison, J. Mol. Biol. 315(4), 887-98; see also the PRIDE server at ICGEB) suitable to scan 40-residue segments of protein chains. The main differences compared to the original PRIDE algorithm are the usage of a bin width of 0.5 A and no limit on the maximum number of bins. Searching PDB Select (2002 April update), the following two interesting cases were found (structures where the three antiparalel β-strands are part of a more extended sheet are generally not considered):
- Tachycitin
PDB ID: 1DQC
Reference: Suetake et al. (2000): Chitin-Binding Proteins from Invertebrates and Plants Comprise a Common Chitin-Binding Structural Motif. J. Biol.Chem.275, 17929)
The N-terminal part of this protein is similar to SGCI, whereas the C-terminal is a chitin-binding domain also found in other chitin-binding proteins. The molecule has 5 disulfide brdges from which only one (Cys12-Cys30) can be regarded as analoguous to one in SGCI (Cys4-Cys19).
Structure of tachycitin: the segment similar to SGCI is colored red, the chitin-binding domain is blue. On the second figure, fisulfide bridges are yellow.
Using residues 1-31 from SGCI (PDB code 1KGM, model 5) and 10-40 from tachycitin (PDB code 1DQC, model 1), the following similarity measures were calculated: PRIDE=0.75, backbone RMSD=3.33 A. (These values do not correspond to those of the 40-residue segments used for database scan.)
- Galanthus nivalis mannose-binding lectin
PDB ID: 1NIV
Reference: n: Hester & Wright (1996): The mannose-specific bulb lectin from Galanthus nivalis (snowdrop) binds mono- and dimannosides at distinct sites. Structure analysis of refined complexes at 2.3 A and 3.0 A resolution. J. Mol. Biol. 262, 516
The lectin is a homotertamer with each monomers consisting of three four-stranded β-sheets. Three of the strands is similar to SGCI, the fourth is donated by a separately triplicated part of the sequence. In the tetramer, two units interact by strand exchange (i.e. one β-strand is donated by the neighbouring subunit).
Structure of the mannose-binding lectin chain A: the segment most similar to SGCI is colored red, the fourth β-strand (donated by the separately triplicated N-terminus) is shown in orange. The conserved asparagine in position similar to that of SGCI is yellow, the conserved tryptophane in position similar to that of SGTI is purple. The contacts of these residues are dissimilar to those of the pacifastin family. The only disulfide of the protein is shown on the second figure relatively to another SGCI-like segment of the molecule (colored green).
Using residues 6-34 from SGCI (PDB code 1KGM, model 5) and 52-80 from the mannose-binding lectin (PDB code 1NIV, chain A), the following similarity measures were calculated: PRIDE=0.69, backbone RMSD=2.90 A. (These values do not correspond to those of the 40-residue segments used for database scan.)