PMID- 10029531
OWN - NLM
STAT- MEDLINE
DCOM- 19990316
LR  - 20190816
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 38
IP  - 8
DP  - 1999 Feb 23
TI  - Human cathepsin V functional expression, tissue distribution, electrostatic
      surface potential, enzymatic characterization, and chromosomal localization.
PG  - 2377-85
AB  - Cathepsin V, a thymus and testis-specific human cysteine protease, was expressed 
      in Pichia pastoris, and its physicokinetic properties were determined.
      Recombinant procathepsin V is autocatalytically activated at acidic pH and is
      effectively inhibited by various cysteine protease class-specific inhibitors. The
      S2P2 subsite specificity of cathepsin V was found to be intermediate between
      those of cathepsins S and L. The substrate binding pocket, S2, accepted both
      aromatic and nonaromatic hydrophobic residues, whereas cathepsins L and S
      preferred either an aromatic or nonaromatic hydrophobic residue, respectively. In
      contrast to cathepsin L, but similar to cathepsin S, cathepsin V exhibited only a
      very weak collagenolytic activity. Furthermore, cathepsin V was determined to be 
      significantly more stable at mildly acidic and neutral pH than cathepsin L, but
      distinctly less stable than cathepsin S. A homology structure model of cathepsin 
      V revealed completely different electrostatic potentials on the molecular surface
      when compared with human cathepsin L. The model-based electrostatic potential of 
      human cathepsin V was neutral to weakly positive at and in the vicinity of the
      active site cleft, whereas that of cathepsin L was negative over extended regions
      of the surface. Surprisingly, the electrostatic potential of the human cathepsin 
      V model structure resembled that of the model structure of mouse cathepsin L.
      These differences in the electrostatic potential at the molecular surfaces
      provide a reactivity determinant that may be the source of differences in
      substrate selectivity and pH stability. Cathepsin V was mapped to the chromosomal
      region 9q22.2, a site adjacent to the cathepsin L locus. The high sequence
      identity and the overlapping chromosomal gene loci suggest that both proteases
      evolved from an ancestral cathepsin L-like precursor by gene duplication.
FAU - Bromme, D
AU  - Bromme D
AD  - Department of Human Genetics, Mount Sinai School of Medicine, CUNY, New York
      10029, USA. brommd01@doc.mssm.edu
FAU - Li, Z
AU  - Li Z
FAU - Barnes, M
AU  - Barnes M
FAU - Mehler, E
AU  - Mehler E
LA  - eng
GR  - AR 39191/AR/NIAMS NIH HHS/United States
GR  - AR 41331/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (DNA, Complementary)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.4.- (Cathepsins)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.22.15 (CTSL protein, human)
RN  - EC 3.4.22.15 (Cathepsin L)
RN  - EC 3.4.22.15 (Ctsl protein, mouse)
RN  - EC 3.4.22.43 (CTSV protein, human)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cathepsin L
MH  - Cathepsins/*biosynthesis/*chemistry/genetics/metabolism
MH  - *Chromosomes, Human, Pair 9
MH  - Cloning, Molecular
MH  - Cysteine Endopeptidases/*biosynthesis/*chemistry/genetics/*metabolism
MH  - DNA, Complementary/isolation & purification
MH  - *Endopeptidases
MH  - Enzyme Activation/genetics
MH  - Humans
MH  - Kinetics
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Organ Specificity/genetics
MH  - Pichia/genetics
MH  - RNA, Messenger/metabolism
MH  - Recombinant Proteins/biosynthesis/isolation & purification/metabolism
MH  - Static Electricity
EDAT- 1999/02/25 00:00
MHDA- 1999/02/25 00:01
CRDT- 1999/02/25 00:00
PHST- 1999/02/25 00:00 [pubmed]
PHST- 1999/02/25 00:01 [medline]
PHST- 1999/02/25 00:00 [entrez]
AID - 10.1021/bi982175f [doi]
AID - bi982175f [pii]
PST - ppublish
SO  - Biochemistry. 1999 Feb 23;38(8):2377-85. doi: 10.1021/bi982175f.