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1w08

From Proteopedia

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Revision as of 07:32, 4 April 2018

STRUCTURE OF T70N HUMAN LYSOZYME

Structural highlights

1w08 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:
Related:	133l, 134l, 1b5u, 1b5v, 1b5w, 1b5x, 1b5y, 1b5z, 1b7l, 1b7m, 1b7n, 1b7o, 1b7p, 1b7q, 1b7r, 1b7s, 1bb3, 1bb4, 1bb5, 1c43, 1c45, 1c46, 1c7p, 1cj6, 1cj7, 1cj8, 1cj9, 1ckc, 1ckd, 1ckf, 1ckg, 1ckh, 1d6p, 1d6q, 1di3, 1di4, 1di5, 1eq4, 1eq5, 1eqe, 1gay, 1gaz, 1gb0, 1gb2, 1gb3, 1gb5, 1gb6, 1gb7, 1gb8, 1gb9, 1gbo, 1gbw, 1gbx, 1gby, 1gbz, 1gdw, 1gdx, 1ge0, 1ge1, 1ge2, 1ge3, 1ge4, 1gev, 1gez, 1gf0, 1gf3, 1gf4, 1gf5, 1gf6, 1gf7, 1gf8, 1gf9, 1gfa, 1gfe, 1gfg, 1gfh, 1gfj, 1gfk, 1gfr, 1gft, 1gfu, 1gfv, 1hnl, 1i1z, 1i20, 1i22, 1inu, 1ioc, 1ip1, 1ip2, 1ip3, 1ip4, 1ip5, 1ip6, 1ip7, 1iwt, 1iwu, 1iwv, 1iww, 1iwx, 1iwy, 1iwz, 1ix0, 1iy3, 1iy4, 1jka, 1jkb, 1jkc, 1jkd, 1jsf, 1jwr, 1laa, 1lhh, 1lhi, 1lhj, 1lhk, 1lhl, 1lhm, 1lmt, 1loz, 1lyy, 1lz1, 1lz4, 1lz5, 1lz6, 1lzr, 1lzs, 1op9, 1oua, 1oub, 1ouc, 1oud, 1oue, 1ouf, 1oug, 1ouh, 1oui, 1ouj, 1qsw, 1re2, 1rem, 1rex, 1rey, 1rez, 1tay, 1tby, 1tcy, 1tdy, 1ubz, 1wqm, 1wqn, 1wqo, 1wqp, 1wqq, 1wqr, 1yam, 1yan, 1yao, 1yap, 1yaq, 207l, 208l, 2bqa, 2bqb, 2bqc, 2bqd, 2bqe, 2bqf, 2bqg, 2bqh, 2bqi, 2bqj, 2bqk, 2bql, 2bqm, 2bqn, 2bqo, 2hea, 2heb, 2hec, 2hed, 2hee, 2hef, 2lhm, 2mea, 2meb, 2mec, 2med, 2mee, 2mef, 2meg, 2meh, 2mei, 3lhm
Activity:	Lysozyme, with EC number 3.2.1.17
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[LYSC_HUMAN] Defects in LYZ are a cause of amyloidosis type 8 (AMYL8) [MIM:105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.^[1]

Function

[LYSC_HUMAN] Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents.

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

T70N human lysozyme is the only known naturally occurring destabilised lysozyme variant that has not been detected in amyloid deposits in human patients. Its study and a comparison of its properties with those of the amyloidogenic variants of lysozyme is therefore important for understanding the determinants of amyloid disease. We report here the X-ray crystal structure and the solution dynamics of T70N lysozyme, as monitored by hydrogen/deuterium exchange and NMR relaxation experiments. The X-ray crystal structure shows that a substantial structural rearrangement results from the amino acid substitution, involving residues 45-51 and 68-75 in particular, and gives rise to a concomitant separation of these two loops of up to 6.5A. A marked decrease in the magnitudes of the generalised order parameter (S2) values of the amide nitrogen atom, for residues 70-74, shows that the T70N substitution increases the flexibility of the peptide backbone around the site of mutation. Hydrogen/deuterium exchange protection factors measured by NMR spectroscopy were calculated for the T70N variant and the wild-type protein. The protection factors for many of backbone amide groups in the beta-domain of the T70N variant are decreased relative to those in the wild-type protein, whereas those in the alpha-domain display wild-type-like values. In pulse-labelled hydrogen/deuterium exchange experiments monitored by mass spectrometry, transient but locally cooperative unfolding of the beta-domain of the T70N variant and the wild-type protein was observed, but at higher temperatures than for the amyloidogenic variants I56T and D67H. These findings reveal that such partial unfolding is an intrinsic property of the human lysozyme structure, and suggest that the readiness with which it occurs is a critical feature determining whether or not amyloid deposition occurs in vivo.

Rationalising lysozyme amyloidosis: insights from the structure and solution dynamics of T70N lysozyme.,Johnson RJ, Christodoulou J, Dumoulin M, Caddy GL, Alcocer MJ, Murtagh GJ, Kumita JR, Larsson G, Robinson CV, Archer DB, Luisi B, Dobson CM J Mol Biol. 2005 Sep 30;352(4):823-36. PMID:16126226^[2]

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

References

↑ Pepys MB, Hawkins PN, Booth DR, Vigushin DM, Tennent GA, Soutar AK, Totty N, Nguyen O, Blake CC, Terry CJ, et al.. Human lysozyme gene mutations cause hereditary systemic amyloidosis. Nature. 1993 Apr 8;362(6420):553-7. PMID:8464497 doi:http://dx.doi.org/10.1038/362553a0
↑ Johnson RJ, Christodoulou J, Dumoulin M, Caddy GL, Alcocer MJ, Murtagh GJ, Kumita JR, Larsson G, Robinson CV, Archer DB, Luisi B, Dobson CM. Rationalising lysozyme amyloidosis: insights from the structure and solution dynamics of T70N lysozyme. J Mol Biol. 2005 Sep 30;352(4):823-36. PMID:16126226 doi:10.1016/j.jmb.2005.07.040

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1w08"

@@ Line 1: / Line 1: @@
 ==STRUCTURE OF T70N HUMAN LYSOZYME==
 <StructureSection load='1w08' size='340' side='right' caption='[[1w08]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[133l|133l]], [[134l|134l]], [[1b5u|1b5u]], [[1b5v|1b5v]], [[1b5w|1b5w]], [[1b5x|1b5x]], [[1b5y|1b5y]], [[1b5z|1b5z]], [[1b7l|1b7l]], [[1b7m|1b7m]], [[1b7n|1b7n]], [[1b7o|1b7o]], [[1b7p|1b7p]], [[1b7q|1b7q]], [[1b7r|1b7r]], [[1b7s|1b7s]], [[1bb3|1bb3]], [[1bb4|1bb4]], [[1bb5|1bb5]], [[1c43|1c43]], [[1c45|1c45]], [[1c46|1c46]], [[1c7p|1c7p]], [[1cj6|1cj6]], [[1cj7|1cj7]], [[1cj8|1cj8]], [[1cj9|1cj9]], [[1ckc|1ckc]], [[1ckd|1ckd]], [[1ckf|1ckf]], [[1ckg|1ckg]], [[1ckh|1ckh]], [[1d6p|1d6p]], [[1d6q|1d6q]], [[1di3|1di3]], [[1di4|1di4]], [[1di5|1di5]], [[1eq4|1eq4]], [[1eq5|1eq5]], [[1eqe|1eqe]], [[1gay|1gay]], [[1gaz|1gaz]], [[1gb0|1gb0]], [[1gb2|1gb2]], [[1gb3|1gb3]], [[1gb5|1gb5]], [[1gb6|1gb6]], [[1gb7|1gb7]], [[1gb8|1gb8]], [[1gb9|1gb9]], [[1gbo|1gbo]], [[1gbw|1gbw]], [[1gbx|1gbx]], [[1gby|1gby]], [[1gbz|1gbz]], [[1gdw|1gdw]], [[1gdx|1gdx]], [[1ge0|1ge0]], [[1ge1|1ge1]], [[1ge2|1ge2]], [[1ge3|1ge3]], [[1ge4|1ge4]], [[1gev|1gev]], [[1gez|1gez]], [[1gf0|1gf0]], [[1gf3|1gf3]], [[1gf4|1gf4]], [[1gf5|1gf5]], [[1gf6|1gf6]], [[1gf7|1gf7]], [[1gf8|1gf8]], [[1gf9|1gf9]], [[1gfa|1gfa]], [[1gfe|1gfe]], [[1gfg|1gfg]], [[1gfh|1gfh]], [[1gfj|1gfj]], [[1gfk|1gfk]], [[1gfr|1gfr]], [[1gft|1gft]], [[1gfu|1gfu]], [[1gfv|1gfv]], [[1hnl|1hnl]], [[1i1z|1i1z]], [[1i20|1i20]], [[1i22|1i22]], [[1inu|1inu]], [[1ioc|1ioc]], [[1ip1|1ip1]], [[1ip2|1ip2]], [[1ip3|1ip3]], [[1ip4|1ip4]], [[1ip5|1ip5]], [[1ip6|1ip6]], [[1ip7|1ip7]], [[1iwt|1iwt]], [[1iwu|1iwu]], [[1iwv|1iwv]], [[1iww|1iww]], [[1iwx|1iwx]], [[1iwy|1iwy]], [[1iwz|1iwz]], [[1ix0|1ix0]], [[1iy3|1iy3]], [[1iy4|1iy4]], [[1jka|1jka]], [[1jkb|1jkb]], [[1jkc|1jkc]], [[1jkd|1jkd]], [[1jsf|1jsf]], [[1jwr|1jwr]], [[1laa|1laa]], [[1lhh|1lhh]], [[1lhi|1lhi]], [[1lhj|1lhj]], [[1lhk|1lhk]], [[1lhl|1lhl]], [[1lhm|1lhm]], [[1lmt|1lmt]], [[1loz|1loz]], [[1lyy|1lyy]], [[1lz1|1lz1]], [[1lz4|1lz4]], [[1lz5|1lz5]], [[1lz6|1lz6]], [[1lzr|1lzr]], [[1lzs|1lzs]], [[1op9|1op9]], [[1oua|1oua]], [[1oub|1oub]], [[1ouc|1ouc]], [[1oud|1oud]], [[1oue|1oue]], [[1ouf|1ouf]], [[1oug|1oug]], [[1ouh|1ouh]], [[1oui|1oui]], [[1ouj|1ouj]], [[1qsw|1qsw]], [[1re2|1re2]], [[1rem|1rem]], [[1rex|1rex]], [[1rey|1rey]], [[1rez|1rez]], [[1tay|1tay]], [[1tby|1tby]], [[1tcy|1tcy]], [[1tdy|1tdy]], [[1ubz|1ubz]], [[1wqm|1wqm]], [[1wqn|1wqn]], [[1wqo|1wqo]], [[1wqp|1wqp]], [[1wqq|1wqq]], [[1wqr|1wqr]], [[1yam|1yam]], [[1yan|1yan]], [[1yao|1yao]], [[1yap|1yap]], [[1yaq|1yaq]], [[207l|207l]], [[208l|208l]], [[2bqa|2bqa]], [[2bqb|2bqb]], [[2bqc|2bqc]], [[2bqd|2bqd]], [[2bqe|2bqe]], [[2bqf|2bqf]], [[2bqg|2bqg]], [[2bqh|2bqh]], [[2bqi|2bqi]], [[2bqj|2bqj]], [[2bqk|2bqk]], [[2bql|2bql]], [[2bqm|2bqm]], [[2bqn|2bqn]], [[2bqo|2bqo]], [[2hea|2hea]], [[2heb|2heb]], [[2hec|2hec]], [[2hed|2hed]], [[2hee|2hee]], [[2hef|2hef]], [[2lhm|2lhm]], [[2mea|2mea]], [[2meb|2meb]], [[2mec|2mec]], [[2med|2med]], [[2mee|2mee]], [[2mef|2mef]], [[2meg|2meg]], [[2meh|2meh]], [[2mei|2mei]], [[3lhm|3lhm]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </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=1w08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w08 OCA], [http://pdbe.org/1w08 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w08 RCSB], [http://www.ebi.ac.uk/pdbsum/1w08 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=1w08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w08 OCA], [http://pdbe.org/1w08 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w08 RCSB], [http://www.ebi.ac.uk/pdbsum/1w08 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1w08 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w0/1w08_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w0/1w08_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1w08

From Proteopedia

Revision as of 07:32, 4 April 2018

STRUCTURE OF T70N HUMAN LYSOZYME

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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