Factor Xa: Difference between revisions
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A more recent crystal structure of α-Lytic protease, published in 2006 with 0.82 Å resolution argues against both the his flip mechanism and the presence of a LBHB between His57 and Asp102 (2.755 Å in this structure). Fuhrmann ''et al'' suggests that a LBHB may have been present in the subtilisin strucutre, it is not required for the serine protease mechanism. Instead they state that the chymotrypsin-like proteases may use a network of optimized hydrogen bonds to position the stabilize the tetrahedral intermediate and position the catalytic triad. Ser195 undergoes a shift of ~1Å upon protonation of His57 that destabilizes the His57-Ser195 H-bond. This conformation change would prevent His57 from reprotonating Ser195 leading to regeneration of the substrate.<ref name="subang" /> | A more recent crystal structure of α-Lytic protease, published in 2006 with 0.82 Å resolution argues against both the his flip mechanism and the presence of a LBHB between His57 and Asp102 (2.755 Å in this structure). Fuhrmann ''et al'' suggests that a LBHB may have been present in the subtilisin strucutre, it is not required for the serine protease mechanism. Instead they state that the chymotrypsin-like proteases may use a network of optimized hydrogen bonds to position the stabilize the tetrahedral intermediate and position the catalytic triad. Ser195 undergoes a shift of ~1Å upon protonation of His57 that destabilizes the His57-Ser195 H-bond. This conformation change would prevent His57 from reprotonating Ser195 leading to regeneration of the substrate.<ref name="subang" /> | ||
==3D structures of factor | ==3D structures of factor Xa== | ||
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
{{#tree:id=OrganizedByTopic|openlevels=0| | |||
*Factor Xa | |||
[[1whe]], [[1whf]] – bFX GLA + EGF-like domains – bovine – NMR<br /> | **[[1whe]], [[1whf]] – bFX GLA + EGF-like domains – bovine – NMR<br /> | ||
[[1ccf]], [[1apo]] - bFX EGF-like domain – NMR<br /> | **[[1ccf]], [[1apo]] - bFX EGF-like domain – NMR<br /> | ||
[[1hcg]] - hFX heavy chain catalytic domain + light chain EGF-like domain (residues 129-179) – human<br /> | **[[1hcg]] - hFX heavy chain catalytic domain + light chain EGF-like domain (residues 129-179) – human<br /> | ||
[[1c5m]] - hFX heavy chain catalytic domain + light chain residues 84-179 | **[[1c5m]] - hFX heavy chain catalytic domain + light chain residues 84-179 | ||
*Factor Xa complex with inhibitor | |||
[[2ei6]], [[2ei7]], [[2ei8]], [[2p93]], [[2p94]], [[2p95]], [[2d1j]], [[1wu1]], [[1v3x]] – hFX heavy chain residues 16-243 + light chain EGF-like domain + inhibitor<br /> | **[[2ei6]], [[2ei7]], [[2ei8]], [[2p93]], [[2p94]], [[2p95]], [[2d1j]], [[1wu1]], [[1v3x]] – hFX heavy chain residues 16-243 + light chain EGF-like domain + inhibitor<br /> | ||
[[2ra0]], [[2p3t]], [[2p16]], [[2p3u]], [[2pr3]], [[2q1j]], [[2g00]], [[2fzz]], [[2bq6]], [[2bq7]], [[2bqw]], [[1z6e]], [[2bmg]], [[2bok]], [[1mq5]], [[1mq6]], [[1fjs]], [[3k9x]], [[3ffg]], [[3kl6]], [[3hpt]], [[2vvc]], [[2vvu]], [[2vvv]], [[2vwl]], [[2vwm]], [[2vwn]], [[2vwo]], [[2w3i]], [[2w3k]], [[2jkh]], [[3ens]], [[2vh6]], [[2vh0]], [[2w26]], [[3cs7]], [[3cen]], [[2phb]], [[2y7x]], [[2y7z]], [[2y80]], [[2y81]], [[2y82]], [[2wyg]], [[2wyj]], [[2xbv]], [[2xbw]], [[2xbx]], [[2xby]], [[1ioe]], [[1iqe]], [[1iqf]], [[1iqg]], [[1iqh]], [[1iqi]], [[1iqj]], [[1iqk]], [[1iql]], [[1iqm]], [[1iqn]], [[1g2l]], [[1g2m]], [[1xka]], [[1xkb]], [[1fax]], [[2y5f]], [[2y5g]], [[2y5h]], [[3q3k]], [[4a7i]], [[3m36]], [[3m37]], [[3tk5]], [[3tk6]] - hFX heavy chain catalytic domain + light chain EGF-like domain + inhibitor<br /> | **[[2ra0]], [[2p3t]], [[2p16]], [[2p3u]], [[2pr3]], [[2q1j]], [[2g00]], [[2fzz]], [[2bq6]], [[2bq7]], [[2bqw]], [[1z6e]], [[2bmg]], [[2bok]], [[1mq5]], [[1mq6]], [[1fjs]], [[3k9x]], [[3ffg]], [[3kl6]], [[3hpt]], [[2vvc]], [[2vvu]], [[2vvv]], [[2vwl]], [[2vwm]], [[2vwn]], [[2vwo]], [[2w3i]], [[2w3k]], [[2jkh]], [[3ens]], [[2vh6]], [[2vh0]], [[2w26]], [[3cs7]], [[3cen]], [[2phb]], [[2y7x]], [[2y7z]], [[2y80]], [[2y81]], [[2y82]], [[2wyg]], [[2wyj]], [[2xbv]], [[2xbw]], [[2xbx]], [[2xby]], [[1ioe]], [[1iqe]], [[1iqf]], [[1iqg]], [[1iqh]], [[1iqi]], [[1iqj]], [[1iqk]], [[1iql]], [[1iqm]], [[1iqn]], [[1g2l]], [[1g2m]], [[1xka]], [[1xkb]], [[1fax]], [[2y5f]], [[2y5g]], [[2y5h]], [[3q3k]], [[4a7i]], [[3m36]], [[3m37]], [[3tk5]], [[3tk6]] - hFX heavy chain catalytic domain + light chain EGF-like domain + inhibitor<br /> | ||
[[2boh]] - hFX heavy chain catalytic domain (mutant) + light chain EGF-like domain (mutant) + inhibitor<br /> | **[[2boh]] - hFX heavy chain catalytic domain (mutant) + light chain EGF-like domain (mutant) + inhibitor<br /> | ||
[[2uwo]], [[2uwp]], [[2uwl]], [[2j94]], [[2j95]], [[2j2u]], [[2j34]], [[2j38]], [[2j4i]], [[2cji]], [[1lqd]], [[1lpg]], [[1lpk]], [[1lpz]], [[1ksn]], [[1ezq]], [[1f0r]], [[1f0s]] - hFX heavy chain catalytic domain + light chain GLA and EGF-like domains + inhibitor<br /> | **[[2uwo]], [[2uwp]], [[2uwl]], [[2j94]], [[2j95]], [[2j2u]], [[2j34]], [[2j38]], [[2j4i]], [[2cji]], [[1lqd]], [[1lpg]], [[1lpk]], [[1lpz]], [[1ksn]], [[1ezq]], [[1f0r]], [[1f0s]] - hFX heavy chain catalytic domain + light chain GLA and EGF-like domains + inhibitor<br /> | ||
[[1nfu]], [[1nfw]], [[1nfx]], [[1nfy]] - hFX heavy chain catalytic domain + light chain residues 46-240 + inhibitor<br /> | **[[1nfu]], [[1nfw]], [[1nfx]], [[1nfy]] - hFX heavy chain catalytic domain + light chain residues 46-240 + inhibitor<br /> | ||
[[3sw2]] - hFX heavy chain catalytic domain + light chain residues 84-179 + inhibitor<br /> | **[[3sw2]] - hFX heavy chain catalytic domain + light chain residues 84-179 + inhibitor<br /> | ||
[[2xc0]], [[2xc4]], [[2xc5]], [[3iit]], [[3kqb]], [[3kqc]], [[3kqd]], [[3kqe]], [[3liw]] - hFX heavy chain catalytic domain + light chain EGF-like domain + inhibitor<br /> | **[[2xc0]], [[2xc4]], [[2xc5]], [[3iit]], [[3kqb]], [[3kqc]], [[3kqd]], [[3kqe]], [[3liw]] - hFX heavy chain catalytic domain + light chain EGF-like domain + inhibitor<br /> | ||
[[4bti]] - hFX heavy chain + light chain + inhibitor<br /> | **[[4bti]] - hFX heavy chain + light chain + inhibitor<br /> | ||
*Factor X binary complex with protein | |||
**[[2h9e]] - hFX heavy chain catalytic domain + light chain residues 86-234 + anti-coagulant protein C2 + DTY-IRL-LPD<br /> | |||
**[[2p3f]] - hFX heavy chain catalytic domain + light chain EGF-like domain + anti-coagulant protein 5<br /> | |||
**[[2gd4]] - hFX heavy chain catalytic domain (mutant) + light chain EGF-like domain + anti-thrombin III (mutant) <br /> | |||
**[[1p0s]] - hFX heavy chain catalytic domain + light chain GLA and EGF-like domains + ecotin precursor (mutant) <br /> | |||
**[[1iod]] – bFX GLA domain + FX-binding protein<br /> | |||
**[[1kig]] - bFX heavy chain catalytic domain + light chain EGF-like domain + anticoagulant peptide<br /> | |||
**[[1fxy]] – hFX/trypsin + PPR-CMK<br /> | |||
**[[4bxw]] – FX catalytic domain + coagulation factor V – brown snake<br /> | |||
}} | |||
==Additional Resources== | ==Additional Resources== | ||
For additional information, see: [[Hemophilia]] | For additional information, see: [[Hemophilia]] | ||