1orf

From Proteopedia

(Difference between revisions)

Revision as of 15:07, 27 October 2021

The Oligomeric Structure of Human Granzyme A Reveals the Molecular Determinants of Substrate Specificity

Structural highlights

1orf is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	GZMA (HUMAN)
Activity:	Granzyme A, with EC number 3.4.21.78
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GRAA_HUMAN] This enzyme is necessary for target cell lysis in cell-mediated immune responses. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Involved in apoptosis.^[1]

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 cell death-inducing serine protease granzyme A (GzmA) has a unique disulfide-linked quaternary structure. The structure of human GzmA bound to a tripeptide CMK inhibitor, determined at a resolution of 2.4 A, reveals that the oligomeric state contributes to substrate selection by limiting access to the active site for potential macromolecular substrates and inhibitors. Unlike other serine proteases, tetrapeptide substrate preferences do not correlate well with natural substrate cleavage sequences. This suggests that the context of the cleavage sequence within a macromolecular substrate imposes another level of selection not observed with the peptide substrates. Modeling of inhibitors bound to the GzmA active site shows that the dimer also contributes to substrate specificity in a unique manner by extending the active-site cleft. The crystal structure, along with substrate library profiling and mutagenesis, has allowed us to identify and rationally manipulate key components involved in GzmA substrate specificity.

The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity.,Bell JK, Goetz DH, Mahrus S, Harris JL, Fletterick RJ, Craik CS Nat Struct Biol. 2003 Jul;10(7):527-34. PMID:12819769^[2]

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

References

↑ Fan Z, Beresford PJ, Zhang D, Xu Z, Novina CD, Yoshida A, Pommier Y, Lieberman J. Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A. Nat Immunol. 2003 Feb;4(2):145-53. Epub 2003 Jan 13. PMID:12524539 doi:10.1038/ni885
↑ Bell JK, Goetz DH, Mahrus S, Harris JL, Fletterick RJ, Craik CS. The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity. Nat Struct Biol. 2003 Jul;10(7):527-34. PMID:12819769 doi:10.1038/nsb944

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='1orf' size='340' side='right'caption='[[1orf]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1orf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ORF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1ORF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1orf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ORF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ORF FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GZMA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GZMA ([https://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/Granzyme_A Granzyme A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.78 3.4.21.78] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Granzyme_A Granzyme A], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.78 3.4.21.78] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1orf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1orf OCA], [http://pdbe.org/1orf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1orf RCSB], [http://www.ebi.ac.uk/pdbsum/1orf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1orf ProSAT]</span></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=1orf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1orf OCA], [https://pdbe.org/1orf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1orf RCSB], [https://www.ebi.ac.uk/pdbsum/1orf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1orf ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GRAA_HUMAN GRAA_HUMAN]] This enzyme is necessary for target cell lysis in cell-mediated immune responses. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Involved in apoptosis.<ref>PMID:12524539</ref>
+[[https://www.uniprot.org/uniprot/GRAA_HUMAN GRAA_HUMAN]] This enzyme is necessary for target cell lysis in cell-mediated immune responses. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Involved in apoptosis.<ref>PMID:12524539</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1orf

From Proteopedia

Revision as of 15:07, 27 October 2021

The Oligomeric Structure of Human Granzyme A Reveals the Molecular Determinants of Substrate Specificity

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox