PMID- 35777236
OWN - NLM
STAT- MEDLINE
DCOM- 20220815
LR  - 20220816
IS  - 1090-2120 (Electronic)
IS  - 0045-2068 (Linking)
VI  - 127
DP  - 2022 Oct
TI  - Investigation of binding mechanism for human plasminogen Kringle 5 with its 
      potential receptor vWA1 domain in Cochlin by bio-specific technologies and 
      molecular dynamic simulation.
PG  - 105989
LID - S0045-2068(22)00395-9 [pii]
LID - 10.1016/j.bioorg.2022.105989 [doi]
AB  - Given the significant clinical potential of human plasminogen Kringle 5 on 
      tumours, it is crucial to seek its receptors for a thorough comprehension of its 
      physiological functions and mechanism. Eleven candidates have been screened out 
      in our previous works. In the present work, we further inquired whether the 
      candidate, von Willebrand factor type A domain 1 in coagulation factor C homology 
      protein (abbr. vWA1), was a potential receptor of Kringle 5, and investigated 
      their binding mechanism by bio-specific experiments, frontal affinity analysis 
      (FA), and molecular dynamic simulation (MDS). After the potential was validated 
      by bio-specific experiments, the FA results stated that vWA1 exhibited a strong 
      interaction towards Kringle 5 in the proportion of 1:1 with the binding constant 
      of 4.18 x 10(4) L/mol. The MDS results showed that the binding was mainly driven 
      by electrostatic and Van der Waals forces and occurred spontaneously, during 
      which vWA1 and Kringle 5 mutually fit each other by conformational changing into 
      more flexible and suitable structures including fluctuations for five loops and 
      partial transformation into a random coil for alpha6-helix in vWA1. Moreover, lysine 
      binding site Leu71-Tyr74 was speculated responsible for Kringle 5 in binding and 
      Tyr72 to be the key amino acid residue. In short, this work not only confirmed 
      vWA1 as a potential Kringle 5 receptor but also provided valuable information on 
      the detailed binding, facilitating the application development of Kringle 5 in 
      regulating immune or inhibiting tumour migration through vWA1.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Zhang, Jiaxin
AU  - Zhang J
AD  - Key laboratory of Resource Biology and Biotechnology in Western China, Mnistry of 
      Education, College of Life Sciences, Northwest University, Xi'an 710069, China.
FAU - Wang, Zhuanhong
AU  - Wang Z
AD  - Key laboratory of Resource Biology and Biotechnology in Western China, Mnistry of 
      Education, College of Life Sciences, Northwest University, Xi'an 710069, China.
FAU - Wang, Jing
AU  - Wang J
AD  - Key laboratory of Resource Biology and Biotechnology in Western China, Mnistry of 
      Education, College of Life Sciences, Northwest University, Xi'an 710069, China.
FAU - Zhang, Ruxue
AU  - Zhang R
AD  - Key laboratory of Resource Biology and Biotechnology in Western China, Mnistry of 
      Education, College of Life Sciences, Northwest University, Xi'an 710069, China.
FAU - Dong, Xiaoting
AU  - Dong X
AD  - Key laboratory of Resource Biology and Biotechnology in Western China, Mnistry of 
      Education, College of Life Sciences, Northwest University, Xi'an 710069, China.
FAU - Bian, Liujiao
AU  - Bian L
AD  - Key laboratory of Resource Biology and Biotechnology in Western China, Mnistry of 
      Education, College of Life Sciences, Northwest University, Xi'an 710069, China. 
      Electronic address: bianliujiao@sohu.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220627
PL  - United States
TA  - Bioorg Chem
JT  - Bioorganic chemistry
JID - 1303703
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Ligands)
RN  - 0 (Peptide Fragments)
RN  - 0 (VWA1 protein, human)
RN  - 0 (plasminogen kringle 5)
RN  - 9001-91-6 (Plasminogen)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - *Extracellular Matrix Proteins
MH  - Humans
MH  - Ligands
MH  - Magnetic Resonance Spectroscopy
MH  - *Molecular Dynamics Simulation
MH  - Peptide Fragments
MH  - Plasminogen
MH  - Protein Binding
MH  - Protein Conformation
OTO - NOTNLM
OT  - Binding mechanism
OT  - Bio-specific technology
OT  - Conformational change
OT  - Frontal affinity analysis
OT  - Kringle 5
OT  - Molecular dynamic simulation
OT  - Receptor
OT  - vWA1 domain in Cochlin
EDAT- 2022/07/02 06:00
MHDA- 2022/08/16 06:00
CRDT- 2022/07/01 18:24
PHST- 2022/03/29 00:00 [received]
PHST- 2022/05/25 00:00 [revised]
PHST- 2022/06/23 00:00 [accepted]
PHST- 2022/07/02 06:00 [pubmed]
PHST- 2022/08/16 06:00 [medline]
PHST- 2022/07/01 18:24 [entrez]
AID - S0045-2068(22)00395-9 [pii]
AID - 10.1016/j.bioorg.2022.105989 [doi]
PST - ppublish
SO  - Bioorg Chem. 2022 Oct;127:105989. doi: 10.1016/j.bioorg.2022.105989. Epub 2022 
      Jun 27.