View source for 1uma

[[Image:1uma.gif|left|200px]]<br />
<applet load="1uma" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="1uma, resolution 2.0&Aring;" />
'''ALPHA-THROMBIN (HIRUGEN) COMPLEXED WITH NA-(N,N-DIMETHYLCARBAMOYL)-ALPHA-AZALYSINE'''<br />

==Overview==
Kinetics for the hydrolysis of the chromogenic active site titrant N, alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester, (Dmc-azaLys-ONp) catalyzed by bovine beta-trypsin, bovine alpha-thrombin, human alpha-thrombin, human Lys77-plasmin, human urinary kallikrein, the, M(r) 33,000 and M(r) 54,000 species of human urokinase, as well as by, porcine pancreatic beta-kallikrein-A and B have been obtained between pH, 6.0 and 8.0, at 21.0 degrees C. Moreover, the three dimensional structure, of the human alpha-thrombin-(hirugen).Dmc-azaLys acyl.enzyme complex has, been analyzed and refined by X-ray crystallography at 2.0 A resolution, (R-factor = 0.168). As observed for bovine beta-trypsin, the acylating, inhibitor molecule is covalently bound to the Ser195 catalytic residue, filling the human alpha-thrombin S1 primary specificity subsite with its, lysyl side-group. However, the carbonyl group of the scissile human, alpha-thrombin.Dmc-azaLys acyl bond does not occupy properly the oxyanion, binding hole. At variance from the bovine beta-trypsin.Dmc-azaLys, acyl.enzyme structure, a second, not covalently bound, inhibitor molecule, partly shielded by the 60-insertion loop of human alpha-thrombin, is, contacting the enzyme "aryl-binding site".

==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]]

==About this Structure==
1UMA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG and IN2 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UMA OCA]. 

==Reference==
Human alpha-thrombin inhibition by the active site titrant N alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester: a comparative kinetic and X-ray crystallographic study., Nardini M, Pesce A, Rizzi M, Casale E, Ferraccioli R, Balliano G, Milla P, Ascenzi P, Bolognesi M, J Mol Biol. 1996 May 24;258(5):851-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8637015 8637015]
[[Category: Hirudo medicinalis]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Thrombin]]
[[Category: Ascenzi, P.]]
[[Category: Balliano, G.]]
[[Category: Bolognesi, M.]]
[[Category: Casale, E.]]
[[Category: Ferraccioli, R.]]
[[Category: Milla, P.]]
[[Category: Nardini, M.]]
[[Category: Pesce, A.]]
[[Category: Rizzi, M.]]
[[Category: IN2]]
[[Category: NAG]]
[[Category: alpha-thrombin]]
[[Category: hirugen complex (serine protease/inhibitor)]]
[[Category: hydrolase]]
[[Category: kringle]]
[[Category: serine protease]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:36:21 2007''