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3k9m

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Revision as of 08:29, 1 November 2017

Cathepsin B in complex with stefin A

Structural highlights

3k9m is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1stf, 1nb3
Gene:	CTSB, CPSB (HUMAN), CSTA, STF1, STFA (HUMAN)
Activity:	Cathepsin B, with EC number 3.4.22.1
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

[CATB_HUMAN] Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis. [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

Cathepsin B (EC 3.4.22.1) is one of the most versatile human cysteine cathepsins. It is important for intracellular protein degradation under normal conditions and is involved in a number of pathological processes. The occluding loop makes cathepsin B unique among cysteine cathepsins. This approximately 20 residue long insertion imbedded into the papain-like protease scaffold restricts access to the active site cleft and endows cathepsin B with its carboxydipeptidase activity. Nevertheless, the enzyme also exhibits endopeptidase activity and is inhibited by stefins and cystatins. To clarify the structural properties of the occluding loop upon the binding of stefins, we determined the crystal structure of the complex between wild-type human stefin A and wild-type human cathepsin B at 2.6 A resolution. The papain-like part of cathepsin B structure remains unmodified, whereas the occluding loop residues are displaced. The part enclosed by the disulfide bridge containing histidines 110 and 111 (i.e. the 'lasso' part) is rotated by approximately 45 degrees away from its original position. A comparison of the structure of the unliganded cathepsin B with the structure of the proenzyme, its complexes with chagasin and stefin A shows that the magnitude of the shift of the occluding loop is related to the size of the binding region. It is smallest in the procathepsin structures and increases in the series of complexes with stefin A and chagasin, although it has no impact on the binding constant. Hence, cathepsin B can dock inhibitors and certain substrates regardless of the size of the binding region.

Stefin A displaces the occluding loop of cathepsin B only by as much as required to bind to the active site cleft.,Renko M, Pozgan U, Majera D, Turk D FEBS J. 2010 Oct;277(20):4338-45. doi: 10.1111/j.1742-4658.2010.07824.x., Epub 2010 Sep 22. PMID:20860624^[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
↑ Renko M, Pozgan U, Majera D, Turk D. Stefin A displaces the occluding loop of cathepsin B only by as much as required to bind to the active site cleft. FEBS J. 2010 Oct;277(20):4338-45. doi: 10.1111/j.1742-4658.2010.07824.x., Epub 2010 Sep 22. PMID:20860624 doi:10.1111/j.1742-4658.2010.07824.x

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/3k9m"

@@ Line 1: / Line 1: @@
 ==Cathepsin B in complex with stefin A==
 <StructureSection load='3k9m' size='340' side='right' caption='[[3k9m]], [[Resolution|resolution]] 2.61&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTSB, CPSB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CSTA, STF1, STFA ([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_B Cathepsin B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.1 3.4.22.1] </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=3k9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k9m OCA], [http://pdbe.org/3k9m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3k9m RCSB], [http://www.ebi.ac.uk/pdbsum/3k9m 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=3k9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k9m OCA], [http://pdbe.org/3k9m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3k9m RCSB], [http://www.ebi.ac.uk/pdbsum/3k9m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3k9m ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 31: / Line 32: @@
 </div>
 <div class="pdbe-citations 3k9m" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Cathepsin|Cathepsin]]
 == References ==
 <references/>

3k9m

From Proteopedia

Revision as of 08:29, 1 November 2017

Cathepsin B in complex with stefin A

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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