4nff: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='4nff' size='340' side='right' caption='[[4nff]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='4nff' size='340' side='right' caption='[[4nff]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4nff]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NFF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NFF FirstGlance]. <br> | <table><tr><td colspan='2'>[[4nff]] 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=4NFF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NFF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nfe|4nfe]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nfe|4nfe]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KLK2 ([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/Tissue_kallikrein Tissue kallikrein], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.35 3.4.21.35] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tissue_kallikrein Tissue kallikrein], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.35 3.4.21.35] </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=4nff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nff OCA], [http://pdbe.org/4nff PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nff RCSB], [http://www.ebi.ac.uk/pdbsum/4nff PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nff ProSAT]</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=4nff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nff OCA], [http://pdbe.org/4nff PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nff RCSB], [http://www.ebi.ac.uk/pdbsum/4nff PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nff ProSAT]</span></td></tr> | ||
| Line 24: | Line 25: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Tissue kallikrein]] | [[Category: Tissue kallikrein]] | ||
[[Category: Brandstetter, H]] | [[Category: Brandstetter, H]] | ||
Revision as of 13:05, 15 November 2017
Structural highlights
Function[KLK2_HUMAN] Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. Publication Abstract from PubMedHuman kallikrein-related peptidase (KLK) 2 is a tryptic serine protease predominantly expressed in prostatic tissue and secreted into prostatic fluid, a major component of seminal fluid. Most likely, it activates and complements chymotryptic KLK3 (prostate-specific antigen) in cleaving seminal clotting proteins, resulting in sperm liquefaction. KLK2 belongs to the "classical" KLKs 1-3, which share an extended 99- or kallikrein loop near their non-primed substrate binding site. Here, we report the 1.9 A crystal structures of two KLK2-small molecule inhibitor complexes. In both structures, discontinuous electron density for the 99-loop indicates that this loop is largely disordered. We provide evidence that the 99-loop is responsible for two biochemical peculiarities of KLK2, i.e. reversible inhibition by micromolar Zn2+ concentrations and permanent inactivation by autocatalytic cleavage. Indeed, several 99-loop mutants of KLK2 displayed an altered susceptibility to Zn2+, which located the Zn2+ binding site at the 99-loop/active site interface. In addition, we identified an autolysis site between residues 95e and 95f in the 99-loop, whose elimination prevented the mature enzyme from limited autolysis and irreversible inactivation. An exhaustive comparison of KLK2 with related structures revealed that in the KLK family, the 99-, 148- and 220-loop exist in open and closed conformations, allowing or preventing substrate access, which extends the concept of conformational selection in trypsin-related proteases. Taken together, our novel biochemical and structural data on KLK2 identify its 99-loop as a key player in activity regulation. Structure-Function Analyses of Human Kallikrein-Related Peptidase 2 Establish the 99-Loop as Master Regulator of Activity.,Skala W, Utzschneider DT, Magdolen V, Debela M, Guo S, Craik CS, Brandstetter H, Goettig P J Biol Chem. 2014 Oct 16. pii: jbc.M114.598201. PMID:25326387[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||||