The entry DI2010015 describes the same interaction with the disordered partner bearing different post-translational modification(s).
Database Accession: DI2010016
Name: Complex of human alpha-thrombin and acetylated recombinant hirudin
PDB ID: 1c1u
Experimental method: X-ray (1.75 Å)
Source organism: Hirudo medicinalis / Homo sapiens
Proof of disorder:
Primary publication of the structure:
Katz BA, Clark JM, Finer-Moore JS, Jenkins TE, Johnson CR, Ross MJ, Luong C, Moore WR, Stroud RM
Design of potent selective zinc-mediated serine protease inhibitors.
(1998) Nature 391: 608-12
PMID: 9468142
Abstract:
Many serine proteases are targets for therapeutic intervention because they often play key roles in disease. Small molecule inhibitors of serine proteases with high affinity are especially interesting as they could be used as scaffolds from which to develop drugs selective for protease targets. One such inhibitor is bis(5-amidino-2-benzimidazolyl)methane (BABIM), standing out as the best inhibitor of trypsin (by a factor of over 100) in a series of over 60 relatively closely related analogues. By probing the structural basis of inhibition, we discovered, using crystallographic methods, a new mode of high-affinity binding in which a Zn2+ ion is tetrahedrally coordinated between two chelating nitrogens of BABIM and two active site residues, His57 and Ser 195. Zn2+, at subphysiological levels, enhances inhibition by over 10(3)-fold. The distinct Zn2+ coordination geometry implies a strong dependence of affinity on substituents. This unique structural paradigm has enabled development of potent, highly selective, Zn2+-dependent inhibitors of several therapeutically important serine proteases, using a physiologically ubiquitous metal ion.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.Molecular function: not assigned
Biological process:
negative regulation of proteolysis Any process that stops, prevents, or reduces the frequency, rate or extent of the hydrolysis of a peptide bond or bonds within a protein.
Cellular component:
Structural annotations of the participating protein chains.Entry contents: 3 distinct polypeptide molecules
Chains: I, H, L
Notes: No modifications of the original PDB file.
Name: Hirudin-2
Source organism: Hirudo medicinalis
Length: 11 residues
Sequence:Sequence according to PDB SEQRESDFEEIPEEYLQ
The sequence contains the following modified/non-standard residues:
• O-sulfo-L-tyrosine (Y) at position 63 (PDB position: 63)
UniProtKB AC: P28504 (positions: 55-65) Coverage: 16.9%
UniRef90 AC: UniRef90_P09945 (positions: 55-65)
Name: Prothrombin
Source organism: Homo sapiens
Length: 259 residues
Sequence:Sequence according to PDB SEQRESIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE
UniProtKB AC: P00734 (positions: 364-622) Coverage: 41.6%
UniRef90 AC: UniRef90_P00734 (positions: 364-622)
Name: Prothrombin
Source organism: Homo sapiens
Length: 36 residues
Sequence:Sequence according to PDB SEQRESTFGSGEADCGLRPLFEKKSLEDKTERELLESYIDGR
UniProtKB AC: P00734 (positions: 328-363) Coverage: 5.8%
UniRef90 AC: UniRef90_P00734 (positions: 328-363)
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Chain I:
The interacting region of hirudin has been shown to be intrinsically disordered (PMID: 1335515). The 50-65 region described in DisProt entry DP00137 covers 25% of the sequence present in the structure.
Chain H:
Thrombin consists of a large and a small subunit. Trypsin domain of the large subunit involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00089). A solved structure of the thrombin dimer is represented by PDB ID 1jou.
Chain L:
Thrombin consists of a large and a small subunit. Trypsin domain of the large subunit involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00089). A solved structure of the thrombin dimer is represented by PDB ID 1jou.
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). The structure can be rotated by left click and hold anywhere on the structure. Representation options can be edited by right clicking on the structure window.
