PMID- 23192025
OWN - NLM
STAT- MEDLINE
DCOM- 20130514
LR  - 20240506
IS  - 1744-3091 (Electronic)
IS  - 1744-3091 (Linking)
VI  - 68
IP  - Pt 12
DP  - 2012 Dec 1
TI  - Complex of myoglobin with phenol bound in a proximal cavity.
PG  - 1465-71
LID - 10.1107/S1744309112045514 [doi]
AB  - Sperm whale myoglobin (Mb) has weak dehaloperoxidase activity and catalyzes the 
      peroxidative dehalogenation of 2,4,6-trichlorophenol (TCP) to 
      2,6-dichloroquinone. Crystals of Mb and of its more active G65T variant were used 
      to study the binding of TCP, 4-iodophenol (4-IP) and phenol. The structures of 
      crystals soaked overnight in a 10 mM solution of phenol revealed that a phenol 
      molecule binds in the proximal cavity, forming a hydrogen bond to the hydroxyl of 
      Tyr146 and hydrophobic contacts which include interactions with Cbeta and Cgamma of the 
      proximal histidine His93. The phenol position corresponds to the strongest xenon 
      binding site, Xe1. It appears that the ligand enters the proximal cavity through 
      a gate formed by the flexible loops 79-86 and 93-103. TCP and 4-IP do not bind to 
      Mb in this manner under similar conditions; however, it appears to be likely that 
      dimethyl sulfoxide (DMSO), which was used at a concentration of 0.8 M to 
      facilitate 4-IP dissolution, binds in the phenol/Xe1 binding site. In this 
      structure, a water molecule coordinated to the heme iron was replaced by an 
      oxygen molecule, reflecting the reduction of the heme. Crystals of Mb and G65T Mb 
      soaked for 5-10 min did not show bound phenol. Kinetic studies of TCP 
      dechlorination showed that phenol has a dual effect: it acts as a competitive 
      inhibitor that is likely to interfere with TCP binding at the heme edge and as a 
      weak activator, likely through binding in the proximal cavity. The lack of phenol 
      bound at the heme edge in the crystal structures suggests that its inhibitory 
      binding only takes place when the heme is activated by hydrogen peroxide.
FAU - Huang, Xiao
AU  - Huang X
AD  - Department of Chemistry and Biochemistry, University of South Carolina, Columbia, 
      SC 20208, USA.
FAU - Wang, Chunxue
AU  - Wang C
FAU - Celeste, Lesa R
AU  - Celeste LR
FAU - Lovelace, Leslie L
AU  - Lovelace LL
FAU - Sun, Shenfang
AU  - Sun S
FAU - Dawson, John H
AU  - Dawson JH
FAU - Lebioda, Lukasz
AU  - Lebioda L
LA  - eng
SI  - PDB/3U3E
SI  - PDB/4H07
SI  - PDB/4H0B
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20121119
PL  - England
TA  - Acta Crystallogr Sect F Struct Biol Cryst Commun
JT  - Acta crystallographica. Section F, Structural biology and crystallization 
      communications
JID - 101226117
RN  - 0 (Chlorophenols)
RN  - 0 (Iodobenzenes)
RN  - 0 (Ligands)
RN  - 0 (Myoglobin)
RN  - 339NCG44TV (Phenol)
RN  - 42VZT0U6YR (Heme)
RN  - 540-38-5 (4-iodophenol)
RN  - MHS8C5BAUZ (2,4,6-trichlorophenol)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Chlorophenols/chemistry/metabolism
MH  - Crystallography, X-Ray
MH  - Heme/chemistry/metabolism
MH  - Hydrogen Bonding
MH  - Iodobenzenes/chemistry/metabolism
MH  - Kinetics
MH  - Ligands
MH  - Myoglobin/*chemistry/metabolism
MH  - Phenol/chemistry/*metabolism
MH  - Protein Conformation
MH  - Sperm Whale/metabolism
PMC - PMC3509966
EDAT- 2012/11/30 06:00
MHDA- 2013/05/15 06:00
PMCR- 2014/11/19
CRDT- 2012/11/30 06:00
PHST- 2012/10/04 00:00 [received]
PHST- 2012/11/03 00:00 [accepted]
PHST- 2012/11/30 06:00 [entrez]
PHST- 2012/11/30 06:00 [pubmed]
PHST- 2013/05/15 06:00 [medline]
PHST- 2014/11/19 00:00 [pmc-release]
AID - S1744309112045514 [pii]
AID - en5522 [pii]
AID - 10.1107/S1744309112045514 [doi]
PST - ppublish
SO  - Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Dec 1;68(Pt 12):1465-71. 
      doi: 10.1107/S1744309112045514. Epub 2012 Nov 19.