1uuc

From Proteopedia

(Difference between revisions)

Revision as of 08:09, 28 March 2018

solution structure of a chimeric LEKTI-domain

Structural highlights

1uuc is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1hdl, 1h0z
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ISK5_HUMAN] Defects in SPINK5 are the cause of Netherton syndrome (NETH) [MIM: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.^[1]

Function

[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.^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The conversion of an alpha-helical to a beta-strand conformation and the presence of chameleon sequences are fascinating from the perspective that such structural features are implicated in the induction of amyloid-related fatal diseases. In this study, we have determined the solution structure of a chimeric domain (Dom1PI) from the multidomain Kazal-type serine proteinase inhibitor LEKTI using multidimensional NMR spectroscopy. This chimeric protein was constructed to investigate the reasons for differences in the folds of the homologous LEKTI domains 1 and 6 [Lauber, T., et al. (2003) J. Mol. Biol. 328, 205-219]. In Dom1PI, two adjacent phenylalanine residues (F28 and F29) of domain 1 were substituted with proline and isoleucine, respectively, as found in the corresponding P4' and P5' positions of domain 6. The three-dimensional structure of Dom1PI is significantly different from the structure of domain 1 and closely resembles the structure of domain 6, despite the sequence being identical to that of domain 1 except for the two substituted phenylalanine residues and being only 31% identical to the sequence of domain 6. The mutation converted a short 3(10)-helix into an extended loop conformation and parts of the long COOH-terminal alpha-helix of domain 1 into a beta-hairpin structure. The latter conformational change occurs in a sequence stretch distinct from the region containing the substituted residues. Therefore, this switch from an alpha-helical structure to a beta-hairpin structure indicates a chameleon sequence of seven residues. We conclude that the secondary structure of Dom1PI is determined not only by the local protein sequence but also by nonlocal interactions.

The solution structure of a chimeric LEKTI domain reveals a chameleon sequence.,Tidow H, Lauber T, Vitzithum K, Sommerhoff CP, Rosch P, Marx UC Biochemistry. 2004 Sep 7;43(35):11238-47. PMID:15366933^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chavanas S, Bodemer C, Rochat A, Hamel-Teillac D, Ali M, Irvine AD, Bonafe JL, Wilkinson J, Taieb A, Barrandon Y, Harper JI, de Prost Y, Hovnanian A. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet. 2000 Jun;25(2):141-2. PMID:10835624 doi:10.1038/75977
↑ Magert HJ, Standker L, Kreutzmann P, Zucht HD, Reinecke M, Sommerhoff CP, Fritz H, Forssmann WG. LEKTI, a novel 15-domain type of human serine proteinase inhibitor. J Biol Chem. 1999 Jul 30;274(31):21499-502. PMID:10419450
↑ Deraison C, Bonnart C, Lopez F, Besson C, Robinson R, Jayakumar A, Wagberg F, Brattsand M, Hachem JP, Leonardsson G, Hovnanian A. LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction. Mol Biol Cell. 2007 Sep;18(9):3607-19. Epub 2007 Jun 27. PMID:17596512 doi:10.1091/mbc.E07-02-0124
↑ Bennett K, Callard R, Heywood W, Harper J, Jayakumar A, Clayman GL, Di WL, Mills K. New role for LEKTI in skin barrier formation: label-free quantitative proteomic identification of caspase 14 as a novel target for the protease inhibitor LEKTI. J Proteome Res. 2010 Aug 6;9(8):4289-94. doi: 10.1021/pr1003467. PMID:20533828 doi:10.1021/pr1003467
↑ Tidow H, Lauber T, Vitzithum K, Sommerhoff CP, Rosch P, Marx UC. The solution structure of a chimeric LEKTI domain reveals a chameleon sequence. Biochemistry. 2004 Sep 7;43(35):11238-47. PMID:15366933 doi:http://dx.doi.org/10.1021/bi0492399

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1uuc"

@@ Line 1: / Line 1: @@
-==SOLUTION STRUCTURE OF A CHIMERIC LEKTI-DOMAIN==
+==solution structure of a chimeric LEKTI-domain==
 <StructureSection load='1uuc' size='340' side='right' caption='[[1uuc]], [[NMR_Ensembles_of_Models | 30 NMR models]]' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1uuc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UUC FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hdl|1hdl]], [[1h0z|1h0z]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uuc OCA], [http://pdbe.org/1uuc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1uuc RCSB], [http://www.ebi.ac.uk/pdbsum/1uuc PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uuc OCA], [http://pdbe.org/1uuc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1uuc RCSB], [http://www.ebi.ac.uk/pdbsum/1uuc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1uuc ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uu/1uuc_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uu/1uuc_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1uuc ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">

1uuc

From Proteopedia

Revision as of 08:09, 28 March 2018

solution structure of a chimeric LEKTI-domain

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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