PMID- 20718866
OWN - NLM
STAT- MEDLINE
DCOM- 20101223
LR  - 20101108
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 277
IP  - 18
DP  - 2010 Sep
TI  - Catalytic digestion of human tumor necrosis factor-alpha by antibody heavy chain.
PG  - 3823-32
LID - 10.1111/j.1742-4658.2010.07785.x [doi]
AB  - It has long been an important task to prepare a catalytic antibody capable of 
      digesting a targeting crucial protein that controls specific life functions. 
      Tumor necrosis factor-alpha (TNF-alpha) is a cytokine and an important molecule concerned 
      with autoimmune diseases such as rheumatoid arthritis, chronic obstructive 
      pulmonary disease, and Crohn's disease. A mAb (ETNF-6 mAb) raised against human 
      TNF-alpha was prepared, and the steric conformation was created by using molecular 
      modeling after the cDNA was sequenced. The heavy chain (ETNF-6-H) of the mAb was 
      considered to possess a catalytic triad-like structure in the complementarity 
      determining regions (CDRs). As a result, ETNF-6-H exhibited a peptidase and a 
      protease activity. In fact, ETNF-6-H predominantly cleaved the Ser5-Arg6 bond of 
      TNF-alpha at the first step, resulting in the generation of a fragment of  approximately  17 kDa. 
      This fragment was digested to a smaller molecule of 15 kDa by scission of the 
      Gln21-Ala22 bond. The intermediate product was further converted into a fragment 
      of 13.3 kDa by successive cleavage of the Leu36-Leu37 and Asn39-Gly40 bonds. The 
      heavy chain possessed a protease activity against TNF-alpha with a multicleavage 
      site.
CI  - (c) 2010 The Authors Journal compilation (c) 2010 FEBS.
FAU - Hifumi, Emi
AU  - Hifumi E
AD  - Research Center for Applied Medical Engineering, Oita University, Oita, Japan.
FAU - Higashi, Kyohei
AU  - Higashi K
FAU - Uda, Taizo
AU  - Uda T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100816
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Antibodies, Catalytic)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Immunoglobulin Heavy Chains)
RN  - 0 (Peptides)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Catalytic/chemistry/immunology/isolation & purification/*metabolism
MH  - Antibodies, Monoclonal/chemistry/*immunology/isolation & purification/*metabolism
MH  - Antibody Affinity
MH  - Base Sequence
MH  - Biocatalysis
MH  - Cross Reactions
MH  - Female
MH  - Humans
MH  - Hydrolysis
MH  - Immunoglobulin Heavy Chains/chemistry/immunology/isolation & 
      purification/*metabolism
MH  - Kinetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Sequence Data
MH  - Peptides/chemistry/metabolism
MH  - Protein Conformation
MH  - Substrate Specificity
MH  - Tumor Necrosis Factor-alpha/*immunology/*metabolism
EDAT- 2010/08/20 06:00
MHDA- 2010/12/25 06:00
CRDT- 2010/08/20 06:00
PHST- 2010/08/20 06:00 [entrez]
PHST- 2010/08/20 06:00 [pubmed]
PHST- 2010/12/25 06:00 [medline]
AID - EJB7785 [pii]
AID - 10.1111/j.1742-4658.2010.07785.x [doi]
PST - ppublish
SO  - FEBS J. 2010 Sep;277(18):3823-32. doi: 10.1111/j.1742-4658.2010.07785.x. Epub 
      2010 Aug 16.