5mhh

From Proteopedia

(Difference between revisions)

Revision as of 08:50, 27 December 2017

Crystal structure of engineered human lipocalin 2 carrying p-boronophenylalanine at position 36

Structural highlights

5mhh 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:
NonStd Res:
Gene:	LCN2, HNL, NGAL (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NGAL_HUMAN] Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity, possibly by sequestrating iron, leading to limit bacterial growth.^[1]

Publication Abstract from PubMed

The molecular recognition of carbohydrates plays a fundamental role in many biological processes. However, the development of carbohydrate-binding reagents for biomedical research and use poses a challenge due to the generally poor affinity of proteins towards sugars in aqueous solution. Here, we describe the effective molecular recognition of pyranose monosaccharides (in particular, galactose and mannose) by a rationally designed protein receptor based on the human lipocalin scaffold (Anticalin). Complexation relies on reversible covalent cis-diol boronate diester formation with a genetically encoded L-boronophenylalanine (Bpa) residue which was incorporated as a non-natural amino acid at a sterically permissive position in the binding site of the Anticalin, as confirmed by X-ray crystallography. Com-pared with the metal-ion and/or avidity-dependent oligovalent lectins that prevail in nature, our approach offers a novel and promising route to generate tight sugar-binding reagents both as research reagents and for biomedical applications.

Rational Design of an Anticalin-Type Sugar-Binding Protein Using a Genetically Encoded Boronate Side Chain.,Edwardraja S, Eichinger A, Theobald I, Sommer CA, Reichert AJ, Skerra A ACS Synth Biol. 2017 Sep 22. doi: 10.1021/acssynbio.7b00199. PMID:28937743^[2]

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

References

↑ Yang J, Goetz D, Li JY, Wang W, Mori K, Setlik D, Du T, Erdjument-Bromage H, Tempst P, Strong R, Barasch J. An iron delivery pathway mediated by a lipocalin. Mol Cell. 2002 Nov;10(5):1045-56. PMID:12453413
↑ Edwardraja S, Eichinger A, Theobald I, Sommer CA, Reichert AJ, Skerra A. Rational Design of an Anticalin-Type Sugar-Binding Protein Using a Genetically Encoded Boronate Side Chain. ACS Synth Biol. 2017 Sep 22. doi: 10.1021/acssynbio.7b00199. PMID:28937743 doi:http://dx.doi.org/10.1021/acssynbio.7b00199

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5mhh"

@@ Line 3: / Line 3: @@
 <StructureSection load='5mhh' size='340' side='right' caption='[[5mhh]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5mhh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MHH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MHH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5mhh]] 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=5MHH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MHH FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=7N8:'>7N8</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LCN2, HNL, NGAL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5mhh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mhh OCA], [http://pdbe.org/5mhh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mhh RCSB], [http://www.ebi.ac.uk/pdbsum/5mhh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mhh ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Eichinger, A]]
 [[Category: Skerra, A]]

5mhh

From Proteopedia

Revision as of 08:50, 27 December 2017

Crystal structure of engineered human lipocalin 2 carrying p-boronophenylalanine at position 36

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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