PMID- 21530540
OWN - NLM
STAT- MEDLINE
DCOM- 20110829
LR  - 20110530
IS  - 1089-8638 (Electronic)
IS  - 0022-2836 (Linking)
VI  - 409
IP  - 4
DP  - 2011 Jun 17
TI  - Probing dimerization and structural flexibility of mammalian lipoxygenases by 
      small-angle X-ray scattering.
PG  - 654-68
LID - 10.1016/j.jmb.2011.04.035 [doi]
AB  - Human lipoxygenases (LOXs) and their metabolites have a great impact on human 
      homeostasis and are of interest for targeted drug design. This goal requires 
      detailed knowledge of their structures and an understanding of structure-function 
      relationship. At the moment, there are two complete crystal structures for 
      mammalian LOX [rabbit 12/15LOX (r-12/15LOX) and human 5LOX (h-5LOX)] and a 
      fragment of human 12LOX. The low-resolution structures in solution for various 
      LOX isoforms have brought about controversial results. Here we explored the 
      behavior of r-12/15LOX in aqueous solution under different conditions (salt and 
      pH) by small-angle X-ray scattering (SAXS) and compared it with human 
      platelet-type 12S-LOX (hp-12LOX) and h-5LOX. Thermodynamic calculations 
      concerning the stability of molecular assemblies, thermal motion analysis [TLSMD 
      (translation, libration, and screw rotation motion detection based on 
      crystallographic temperature factor B(j))], and results of SAXS analyses brought 
      about the following conclusions: (i) in contrast to its crystal structure, 
      r-12/15LOX functions as a monomer that dominates in solution; (ii) it dimerizes 
      at higher protein concentrations in the presence of salt and with increasing 
      degree of motional freedom of the N-terminal PLAT domain, as suggested by the 
      Y98,614-->R double mutant; (iii) in aqueous solutions, hp-12LOX is stable as a 
      dimer, in contrast to h-5LOX and r-12/15LOX, which are monomeric; and (iv) all 
      three mammalian isozymes show a high level of flexibility not only for the PLAT 
      domain but also for other subdomains of the catalytic part in TLS (translation, 
      libration, and screw rotation) analysis and hp-12LOX in SAXS.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Shang, Weifeng
AU  - Shang W
AD  - European Molecular Biology Laboratory, Hamburg Outstation, c/o DESY, Notkestrasse 
      85, D-22603 Hamburg, Germany.
FAU - Ivanov, Igor
AU  - Ivanov I
FAU - Svergun, Dmitri I
AU  - Svergun DI
FAU - Borbulevych, Oleg Y
AU  - Borbulevych OY
FAU - Aleem, Ansari M
AU  - Aleem AM
FAU - Stehling, Sabine
AU  - Stehling S
FAU - Jankun, Jerzy
AU  - Jankun J
FAU - Kuhn, Hartmut
AU  - Kuhn H
FAU - Skrzypczak-Jankun, Ewa
AU  - Skrzypczak-Jankun E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110420
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Isoenzymes)
RN  - 0 (Salts)
RN  - 0 (Solutions)
RN  - EC 1.13.11.- (Lipoxygenases)
SB  - IM
MH  - Animals
MH  - Crystallography, X-Ray
MH  - Enzyme Stability
MH  - Homeostasis
MH  - Humans
MH  - Isoenzymes/*chemistry/genetics/metabolism
MH  - Lipoxygenases/*chemistry/genetics/metabolism
MH  - Models, Molecular
MH  - Mutation
MH  - Protein Multimerization
MH  - *Protein Structure, Quaternary
MH  - *Protein Structure, Tertiary
MH  - Rabbits
MH  - Salts/chemistry
MH  - *Scattering, Small Angle
MH  - Solutions/chemistry
MH  - Structure-Activity Relationship
MH  - Thermodynamics
EDAT- 2011/05/03 06:00
MHDA- 2011/08/30 06:00
CRDT- 2011/05/03 06:00
PHST- 2011/01/31 00:00 [received]
PHST- 2011/04/06 00:00 [revised]
PHST- 2011/04/12 00:00 [accepted]
PHST- 2011/05/03 06:00 [entrez]
PHST- 2011/05/03 06:00 [pubmed]
PHST- 2011/08/30 06:00 [medline]
AID - S0022-2836(11)00450-5 [pii]
AID - 10.1016/j.jmb.2011.04.035 [doi]
PST - ppublish
SO  - J Mol Biol. 2011 Jun 17;409(4):654-68. doi: 10.1016/j.jmb.2011.04.035. Epub 2011 
      Apr 20.