View source for 5yhn


==Solution structure of the LEKTI Domain 4==
<StructureSection load='5yhn' size='340' side='right'caption='[[5yhn]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5yhn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YHN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YHN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5yhn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yhn OCA], [https://pdbe.org/5yhn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yhn RCSB], [https://www.ebi.ac.uk/pdbsum/5yhn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yhn ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ISK5_HUMAN ISK5_HUMAN] Defects in SPINK5 are the cause of Netherton syndrome (NETH) [MIM:[https://omim.org/entry/256500 256500]. NETH is an autosomal recessive congenital ichthyosis associated with hair shaft abnormalities and anomalies of the immune system. Typical features are ichthyosis linearis circumflexa, ichthyosiform erythroderma, trichorrhexis invaginata (bamboo hair), atopic dermatitis, and hayfever. High postnatal mortality is due to failure to thrive, infections and hypernatremic dehydration.<ref>PMID:10835624</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ISK5_HUMAN ISK5_HUMAN] Serine protease inhibitor, probably important for the anti-inflammatory and/or antimicrobial protection of mucous epithelia. Contribute to the integrity and protective barrier function of the skin by regulating the activity of defense-activating and desquamation-involved proteases. Inhibits KLK5, it's major target, in a pH-dependent manner. Inhibits KLK7, KLK14 CASP14, and trypsin.<ref>PMID:10419450</ref> <ref>PMID:17596512</ref> <ref>PMID:20533828</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Despite being initially identified in the blood filtrate, LEKTI is a 15-domain Kazal-type inhibitor mostly known in the regulation of skin desquamation. In the current study, screening of serine proteases in blood coagulation cascade showed that LEKTI domain 4 has inhibitory activity toward only FXIa, whereas LEKTI domain 6 inhibits both FXIa and FXaB (bovine FXa). Nuclear magnetic resonance structural and dynamic experiments plus molecular dynamics simulation revealed that LEKTI domain 4 has enhanced backbone flexibility at the reactive-site loop. A model of the LEKTI-protease complex revealed that FXaB has a narrower S4 pocket compared with FXIa and hence prefers only small side-chain residues at the P4 position, such as Ala in LEKTI domain 6. Mutational studies combined with a molecular complex model suggest that both a more flexible reactive-site loop and a bulky residue at the P4 position make LEKTI domain 4 a weaker but highly selective inhibitor of FXIa.

Homologous Lympho-Epithelial Kazal-type Inhibitor Domains Delay Blood Coagulation by Inhibiting Factor X and XI with Differential Specificity.,Ramesh K, Lama D, Tan KW, Nguyen VS, Chew FT, Verma CS, Mok YK Structure. 2018 Jun 13. pii: S0969-2126(18)30205-3. doi:, 10.1016/j.str.2018.05.018. PMID:30017565<ref>PMID:30017565</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5yhn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mok YK]]
[[Category: Ramesh K]]