PMID- 25488402
OWN - NLM
STAT- MEDLINE
DCOM- 20160719
LR  - 20240323
IS  - 1097-0134 (Electronic)
IS  - 0887-3585 (Print)
IS  - 0887-3585 (Linking)
VI  - 83
IP  - 11
DP  - 2015 Nov
TI  - Modulation of HIV protease flexibility by the T80N mutation.
PG  - 1929-39
LID - 10.1002/prot.24737 [doi]
AB  - The flexibility of HIV protease (HIVp) plays a critical role in enabling 
      enzymatic activity and is required for substrate access to the active site. While 
      the importance of flexibility in the flaps that cover the active site is well 
      known, flexibility in other parts of the enzyme is also critical for function. 
      One key region is a loop containing Thr 80, which forms the walls of the active 
      site. Although not situated within the active site, amino acid Thr80 is 
      absolutely conserved. The mutation T80N preserves the structure of the enzyme but 
      catalytic activity is completely lost. To investigate the potential influence of 
      the T80N mutation on HIVp flexibility, wide-angle X-ray scattering (WAXS) data 
      was measured for a series of HIVp variants. Starting with a calculated WAXS 
      pattern from a rigid atomic model, the modulations in the intensity distribution 
      caused by structural fluctuations in the protein were predicted by simple 
      analytic methods and compared with the experimental data. An analysis of T80N 
      WAXS data shows that this variant is significantly more rigid than the WT across 
      all length scales. The effects of this single point mutation extend throughout 
      the protein, to alter the mobility of amino acids in the enzymatic core. These 
      results support the contentions that significant protein flexibility extends 
      throughout HIVp and is critical to catalytic function.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Zhou, Hao
AU  - Zhou H
AD  - Department of Electrical and Computer Engineering, Northeastern University, 
      Boston, Massachusetts.
FAU - Li, Shangyang
AU  - Li S
AD  - Department of Electrical and Computer Engineering, Northeastern University, 
      Boston, Massachusetts.
FAU - Badger, John
AU  - Badger J
AD  - DeltaG Technologies, San Diego, California.
FAU - Nalivaika, Ellen
AU  - Nalivaika E
AD  - Department of Biochemistry and Molecular Pharmacology, University of 
      Massachusetts Medical School, Worcester, Massachusetts.
FAU - Cai, Yufeng
AU  - Cai Y
AD  - Department of Biochemistry and Molecular Pharmacology, University of 
      Massachusetts Medical School, Worcester, Massachusetts.
FAU - Foulkes-Murzycki, Jennifer
AU  - Foulkes-Murzycki J
AD  - Department of Biochemistry and Molecular Pharmacology, University of 
      Massachusetts Medical School, Worcester, Massachusetts.
FAU - Schiffer, Celia
AU  - Schiffer C
AD  - Department of Biochemistry and Molecular Pharmacology, University of 
      Massachusetts Medical School, Worcester, Massachusetts.
FAU - Makowski, Lee
AU  - Makowski L
AD  - Department of Bioengineering, Northeastern University, Boston, Massachusetts.
AD  - Department of Chemistry and Chemical Biology, Northeastern University, Boston, 
      Massachusetts.
LA  - eng
GR  - R01 GM65347/GM/NIGMS NIH HHS/United States
GR  - R01 GM85648/GM/NIGMS NIH HHS/United States
GR  - P01 GM66524/GM/NIGMS NIH HHS/United States
GR  - P41 RR008630/RR/NCRR NIH HHS/United States
GR  - R01GM085648/GM/NIGMS NIH HHS/United States
GR  - R01 GM085648/GM/NIGMS NIH HHS/United States
GR  - P01 GM066524/GM/NIGMS NIH HHS/United States
GR  - R01 GM064347/GM/NIGMS NIH HHS/United States
GR  - P01 GM109767/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20150929
PL  - United States
TA  - Proteins
JT  - Proteins
JID - 8700181
RN  - EC 3.4.23.- (HIV Protease)
SB  - IM
MH  - HIV Protease/*chemistry/genetics/*metabolism
MH  - Molecular Dynamics Simulation
MH  - Mutation
MH  - Pliability
MH  - X-Ray Diffraction
PMC - PMC4461556
MID - NIHMS658775
OTO - NOTNLM
OT  - molecular dynamics simulation
OT  - protein flexibility
OT  - x-ray solution scattering
EDAT- 2014/12/10 06:00
MHDA- 2016/07/20 06:00
PMCR- 2016/11/01
CRDT- 2014/12/10 06:00
PHST- 2014/09/04 00:00 [received]
PHST- 2014/11/17 00:00 [revised]
PHST- 2014/11/26 00:00 [accepted]
PHST- 2014/12/10 06:00 [entrez]
PHST- 2014/12/10 06:00 [pubmed]
PHST- 2016/07/20 06:00 [medline]
PHST- 2016/11/01 00:00 [pmc-release]
AID - 10.1002/prot.24737 [doi]
PST - ppublish
SO  - Proteins. 2015 Nov;83(11):1929-39. doi: 10.1002/prot.24737. Epub 2015 Sep 29.