PMID- 22295093
OWN - NLM
STAT- MEDLINE
DCOM- 20120608
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 1
DP  - 2012
TI  - Biochemical discrimination between selenium and sulfur 1: a single residue 
      provides selenium specificity to human selenocysteine lyase.
PG  - e30581
LID - 10.1371/journal.pone.0030581 [doi]
LID - e30581
AB  - Selenium and sulfur are two closely related basic elements utilized in nature for 
      a vast array of biochemical reactions. While toxic at higher concentrations, 
      selenium is an essential trace element incorporated into selenoproteins as 
      selenocysteine (Sec), the selenium analogue of cysteine (Cys). Sec lyases (SCLs) 
      and Cys desulfurases (CDs) catalyze the removal of selenium or sulfur from Sec or 
      Cys and generally act on both substrates. In contrast, human SCL (hSCL) is 
      specific for Sec although the only difference between Sec and Cys is the identity 
      of a single atom. The chemical basis of this selenium-over-sulfur discrimination 
      is not understood. Here we describe the X-ray crystal structure of hSCL and 
      identify Asp146 as the key residue that provides the Sec specificity. A D146K 
      variant resulted in loss of Sec specificity and appearance of CD activity. A 
      dynamic active site segment also provides the structural prerequisites for direct 
      product delivery of selenide produced by Sec cleavage, thus avoiding release of 
      reactive selenide species into the cell. We thus here define a molecular 
      determinant for enzymatic specificity discrimination between a single selenium 
      versus sulfur atom, elements with very similar chemical properties. Our findings 
      thus provide molecular insights into a key level of control in human selenium and 
      selenoprotein turnover and metabolism.
FAU - Collins, Ruairi
AU  - Collins R
AD  - Structural Genomics Consortium, Department of Medical Biochemistry and 
      Biophysics, Karolinska Institute, Stockholm, Sweden.
FAU - Johansson, Ann-Louise
AU  - Johansson AL
FAU - Karlberg, Tobias
AU  - Karlberg T
FAU - Markova, Natalia
AU  - Markova N
FAU - van den Berg, Susanne
AU  - van den Berg S
FAU - Olesen, Kenneth
AU  - Olesen K
FAU - Hammarstrom, Martin
AU  - Hammarstrom M
FAU - Flores, Alex
AU  - Flores A
FAU - Schuler, Herwig
AU  - Schuler H
FAU - Schiavone, Lovisa Holmberg
AU  - Schiavone LH
FAU - Brzezinski, Peter
AU  - Brzezinski P
FAU - Arner, Elias S J
AU  - Arner ES
FAU - Hogbom, Martin
AU  - Hogbom M
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120125
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 70FD1KFU70 (Sulfur)
RN  - EC 4.- (Lyases)
RN  - EC 4.4.1.16 (selenocysteine lyase)
RN  - H6241UJ22B (Selenium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Catalytic Domain
MH  - Computational Biology
MH  - Conserved Sequence
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Lyases/*chemistry/genetics/*metabolism
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Rats
MH  - Selenium/chemistry/*metabolism
MH  - Substrate Specificity
MH  - Sulfur/*metabolism
PMC - PMC3266270
COIS- Competing Interests: During the study period LHS and KO were not affiliated to 
      AstraZeneca and Nanoxis AB, respectively. These affiliations were made after 
      completion of the study and does not alter the authors' adherence to all the PLoS 
      ONE policies on sharing data and materials.
EDAT- 2012/02/02 06:00
MHDA- 2012/06/09 06:00
PMCR- 2012/01/25
CRDT- 2012/02/02 06:00
PHST- 2011/08/26 00:00 [received]
PHST- 2011/12/19 00:00 [accepted]
PHST- 2012/02/02 06:00 [entrez]
PHST- 2012/02/02 06:00 [pubmed]
PHST- 2012/06/09 06:00 [medline]
PHST- 2012/01/25 00:00 [pmc-release]
AID - PONE-D-11-16669 [pii]
AID - 10.1371/journal.pone.0030581 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(1):e30581. doi: 10.1371/journal.pone.0030581. Epub 2012 Jan 25.