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1nb3

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Revision as of 07:03, 7 February 2018

Crystal structure of stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo-and exopeptidases

Structural highlights

1nb3 is a 12 chain structure with sequence from Human and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1nb5
Gene:	CSTA OR STF1 (HUMAN)
Activity:	Cathepsin H, with EC number 3.4.22.16
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CYTA_HUMAN] Defects in CSTA are the cause of ichthyosis exfoliative autosomal recessive ichthyosis bullosa of Siemens-like (AREI) [MIM:607936]. A form of congenital exfoliative ichthyosis, sharing some features with ichthyosis bullosa of Siemens and annular epidermolytic ichthyosis. AREI presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of non-erythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Electron microscopy analysis of skin biopsies, reveals mostly normal-appearing upper layers of the epidermis, but prominent intercellular edema of the basal and suprabasal cell layers with aggregates of tonofilaments in the basal keratinocytes.^[1]

Function

[CYTA_HUMAN] This is an intracellular thiol proteinase inhibitor. Has an important role in desmosome-mediated cell-cell adhesion in the lower levels of the epidermis.^[2]

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

Binding of cystatin-type inhibitors to papain-like exopeptidases cannot be explained by the stefin B-papain complex. The crystal structure of human stefin A bound to an aminopeptidase, porcine cathepsin H, has been determined in monoclinic and orthorhombic crystal forms at 2.8A and 2.4A resolutions, respectively. The asymmetric unit of each form contains four complexes. The structures are similar to the stefin B-papain complex, but with a few distinct differences. On binding, the N-terminal residues of stefin A adopt the form of a hook, which pushes away cathepsin H mini-chain residues and distorts the structure of the short four residue insertion (Lys155A-Asp155D) unique to cathepsin H. Comparison with the structure of isolated cathepsin H shows that the rims of the cathepsin H structure are slightly displaced (up to 1A) from their position in the free enzyme. Furthermore, comparison with the stefin B-papain complex showed that molecules of stefin A bind about 0.8A deeper into the active site cleft of cathepsin H than stefin B into papain. The approach of stefin A to cathepsin H induces structural changes along the interaction surface of both molecules, whereas no such changes were observed in the stefin B-papain complex. Carboxymethylation of papain seems to have prevented the formation of the genuine binding geometry between a papain-like enzyme and a cystatin-type inhibitor as we observe it in the structure presented here.

Crystal structure of Stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo- and exopeptidases.,Jenko S, Dolenc I, Guncar G, Dobersek A, Podobnik M, Turk D J Mol Biol. 2003 Feb 21;326(3):875-85. PMID:12581647^[3]

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

References

↑ Blaydon DC, Nitoiu D, Eckl KM, Cabral RM, Bland P, Hausser I, van Heel DA, Rajpopat S, Fischer J, Oji V, Zvulunov A, Traupe H, Hennies HC, Kelsell DP. Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell-cell adhesion. Am J Hum Genet. 2011 Oct 7;89(4):564-71. doi: 10.1016/j.ajhg.2011.09.001. Epub, 2011 Sep 22. PMID:21944047 doi:10.1016/j.ajhg.2011.09.001
↑ Blaydon DC, Nitoiu D, Eckl KM, Cabral RM, Bland P, Hausser I, van Heel DA, Rajpopat S, Fischer J, Oji V, Zvulunov A, Traupe H, Hennies HC, Kelsell DP. Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell-cell adhesion. Am J Hum Genet. 2011 Oct 7;89(4):564-71. doi: 10.1016/j.ajhg.2011.09.001. Epub, 2011 Sep 22. PMID:21944047 doi:10.1016/j.ajhg.2011.09.001
↑ Jenko S, Dolenc I, Guncar G, Dobersek A, Podobnik M, Turk D. Crystal structure of Stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo- and exopeptidases. J Mol Biol. 2003 Feb 21;326(3):875-85. PMID:12581647

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/1nb3"

@@ Line 1: / Line 1: @@
 ==Crystal structure of stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo-and exopeptidases==
 <StructureSection load='1nb3' size='340' side='right' caption='[[1nb3]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CSTA OR STF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_H Cathepsin H], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.16 3.4.22.16] </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=1nb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nb3 OCA], [http://pdbe.org/1nb3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1nb3 RCSB], [http://www.ebi.ac.uk/pdbsum/1nb3 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=1nb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nb3 OCA], [http://pdbe.org/1nb3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1nb3 RCSB], [http://www.ebi.ac.uk/pdbsum/1nb3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1nb3 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 17: / Line 18: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nb/1nb3_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nb/1nb3_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 32: / Line 33: @@
 </div>
 <div class="pdbe-citations 1nb3" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Cathepsin|Cathepsin]]
 == References ==
 <references/>

1nb3

From Proteopedia

Revision as of 07:03, 7 February 2018

Crystal structure of stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo-and exopeptidases

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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