View source for 1hlt

[[Image:1hlt.gif|left|200px]]<br />
<applet load="1hlt" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="1hlt, resolution 3.0&Aring;" />
'''THE STRUCTURE OF A NONADECAPEPTIDE OF THE FIFTH EGF DOMAIN OF THROMBOMODULIN COMPLEXED WITH THROMBIN'''<br />

==Overview==
The crystallographic structure has been determined of a complex between a, nonadecapeptide from the fifth epidermal growth factor (EGF5) domain of, human thrombomodulin and human D-PheProArg-alpha-thrombin. The peptide, corresponds to amino acid residues Glu408-Glu426 of thrombomodulin and, contains the third disulfide loop of EGF5 and its linker to EGF6. The, structure was refined at 3.0-A resolution to an R-value of 0.146. There, are two thrombin molecules in the asymmetric unit, and the structure in, the crystal is a 2:1 thrombin complex. The folding of the peptide, corresponds closely to the third disulfide loop of EGF2 of factor Xa (rms, delta = 1.0 A). The peptide is squeezed between cofacial electropositive, fibrinogen recognition exo sites of the two thrombin molecules. Since the, peptide has a total of seven aspartic and glutamic acid residues, the, principal binding interaction with thrombin is electrostatic. A major, hydrophobic association, which is highly directional in such a pronounced, electrostatic environment, involves a TyrIleLeu triplet of the peptide and, Phe34, Leu65, Tyr76, and Ile82 (chymotrypsinogen numbering) of one, thrombin molecule. The tyrosine of the peptide is sandwiched between the, thrombin aromatic rings and is most likely the prime source of the, specificity of the thrombomodulin-thrombin interaction.

==Disease==
Known diseases associated with this structure: Dysprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hyperprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hypoprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Myocardial infarction, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188040 188040]], Thrombophilia due to thrombomodulin defect OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188040 188040]]

==About this Structure==
1HLT is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HLT OCA]. 

==Reference==
Structure of a nonadecapeptide of the fifth EGF domain of thrombomodulin complexed with thrombin., Mathews II, Padmanabhan KP, Tulinksy A, Sadler JE, Biochemistry. 1994 Nov 22;33(46):13547-52. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7947765 7947765]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Mathews, I.I.]]
[[Category: Tulinsky, A.]]
[[Category: CH2]]
[[Category: complex(serine proteinase/inhibitor)]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:20:00 2007''