Page
1
of
8
DRAFT
April
4,
2005
FIFRA
SCIENTIFIC
ADVISORY
PANEL
(
SAP)
OPEN
MEETING
MAY
3­
4,
2005
FIFRA
SAP
WEB
SITE
http://
www.
epa.
gov/
scipoly/
sap/
OPP
Docket
Telephone:
(
703)
305­
5805
Docket
Number:
OPP­
2005­
0060
TSCA
INVENTORY
NOMENCLATURE
FOR
ENZYMES
AND
PROTEINS
TUESDAY,
MAY
3,
2005
Holiday
Inn
 
Rosslyn
at
Key
Bridge
1900
North
Fort
Myer
Drive
Arlington,
Virginia
22209
Telephone:
(
703)
807­
2000

8:
30
AM
Introduction
and
Identification
of
Panel
Members
 
Steven
Heeringa,
Ph.
D.
(
FIFRA
SAP
Session
Chair)


8:
45
AM
Administrative
Procedures
by
Designated
Federal
Official
 
Paul
Lewis,
Ph.
D.


8:
50
AM
Welcome
 
Clifford
Gabriel,
Ph.
D.
(
Director,
Office
of
Science
Coordination
and
Policy,
EPA)


8:
55
AM
Opening
Remarks
 
Mr.
Charles
Auer
(
Director,
Office
of
Pollution
Prevention
and
Toxics,
EPA)


9:
00
AM
Background
on
TSCA
Inventory
 
Greg
Fritz,
Ph.
D.
(
Economics,
Environment
and
Technology
Division,
Office
of
Pollution
Prevention
and
Toxics,
EPA)


9:
30
AM
Agency's
Proposed
Approach
for
Enzyme
Identification
on
the
TSCA
Inventory
­
Mark
Segal,
Ph.
D.
(
Risk
Assessment
Division,
Office
of
Pollution
Prevention
and
Toxics,
EPA)


10:
15
AM
BREAK

10:
30
AM
Public
Comments
EPA
is
proposing
the
use
of
four
data
elements
(
function,
sequence,
source,
and
processing)
for
comprehensively
listing
and
distinguishing
among
enzymes
on
the
TSCA
Inventory.
The
following
questions
are
intended
to
help
the
Agency
make
a
final
decision
on
how
enzymes
will
be
listed
on
the
Inventory
in
the
future.
Page
2
of
8
Function
The
FUNCTION
of
an
enzyme
refers
to
its
catalytic
activity.
Internationally­
accepted
nomenclature
conventions
of
the
Nomenclature
Committee
of
the
International
Union
of
Biochemistry
and
Molecular
Biology
(
NC­
IUBMB)
describe
and
categorize
enzymes
based
on
their
function.
The
NC­
IUBMB
assigns
enzymes
an
Enzyme
Committee
(
EC)
code
number
based
on
the
specific
reaction(
s)
catalyzed
by
the
enzyme,
the
nature
of
the
bond
involved,
and
the
substrate
acted
upon.
EPA
intends
to
incorporate
function
into
TSCA
Inventory
enzyme
listings
by
using
these
EC
codes
and
the
systematic
name
for
the
specific
catalytic
activity.
In
the
questions
below,
please
identify
the
scientific
merit
for
using
function
information
to
differentiate
among
enzymes
and
identify
what
level
of
detail
regarding
function
would
be
scientifically
appropriate
for
this
purpose.

1.
While
the
Agency
recognizes
the
practical,
historical
advantages
of
using
function
to
describe
enzymes,
in
the
context
of
the
Agency's
need
for
unique
and
unambiguous
naming,
what
is
the
scientific
rationale
for
identifying
an
enzyme
based
on
the
chemical
reaction(
s)
it
catalyzes?

2.
How
precise
is
the
IUBMB
EC
categorizing
system
for
describing
enzyme
function?
For
example,
in
addition
to
the
EC
function
category
to
which
an
enzyme
belongs,
what
additional
information
about
enzyme
structure
and/
or
chemical
properties,
if
any,
would
be
gained
by
a
more
detailed
functional
description
that
included
a.
enzyme
reaction
conditions
(
e.
g.,
pH
range,
reaction
temperature
range)?

b.
non­
catalytic
enzyme
functions
that
are
not
represented
by
EC
codes
(
e.
g.,
binding
properties)?

c.
other
additional
information
about
function
that
could
be
used
to
differentiate
enzymes
(
please
specify
what
would
be
of
value)?

3.
The
Agency
is
trying
to
gauge
the
probable
comprehensiveness
of
enzyme
catalytic
function
descriptions
for
subsequent
enzyme
reporting.

a.
How
common
are
multifunctional
enzymes?

b.
How
frequently
are
new
catalytic
functions
for
existing
enzymes
discovered?

c.
How
good
are
existing
models
to
assess
the
likelihood
that
an
enzyme
may
have
several
catalytic
functions?

d.
What
information
is
required
to
utilize
such
models?


12:
30
PM
LUNCH

1:
30
PM
Panel
Discussion
4.
What
information
about
an
enzyme
could
be
gained
by
identifying
it
based
on
its
amino
acid
sequence?

5.
The
Agency
is
trying
to
assess
the
expected
amount
of
variation
in
an
enzyme
amino
acid
sequence
due
to
various
causes
in
spite
of
current
quality
control
standards.
Page
3
of
8
a.
How
much
and
what
type
of
variation
(
including
substitutions,
deletions,
and
additions)
can
be
expected
in
the
amino
acid
sequence
of
an
enzyme
produced
in
multiple
batches
that
will
arise
due
to
unintended
differences
in
production
conditions?
Estimate
a
percentage,
number
of
residues,
or
other
quantifiable
measure
of
variation.

b.
How
much
and
what
type
of
variation
(
including
substitutions,
deletions,
and
additions)
can
be
expected
in
the
amino
acid
sequence
of
an
enzyme
within
a
given
sample
of
a
single
production
batch
due
to
individual­
level
variation
in
an
enzymeproducing
population?
Estimate
a
percentage,
number
of
residues,
or
other
quantifiable
measure
of
variation.

c.
How
much
and
what
type
of
variation
(
including
substitutions,
deletions,
and
additions)
can
be
expected
in
the
amino
acid
sequence
of
an
enzyme
across
multiple
samples
collected
over
time
(
e.
g.,
in
microbial
cultures
stored
for
extended
periods)
due
to
changes
in
an
enzyme­
producing
population?
Estimate
a
percentage,
number
of
residues,
or
other
quantifiable
measure
of
variation.

i..
Over
what
time
scale
will
such
variation
arise?
That
is,
is
there
a
predictable
relationship
between
the
amount
of
variation
and
the
length
of
time
in
culture?

ii.
What
kinds
of
changes
might
occur
to
an
enzyme
preparation
if
naturally
occurring
variants
become
the
dominant
component
(
e.
g.,
changes
in
rates
of
activity,
reactions
catalyzed,
substrate
range,
response
to
environmental
conditions)?

iii.
Have
any
enzymes
in
commerce
or
research
been
known
to
change
in
amino
acid
sequence
over
time?
Have
any
been
known
to
remain
unchanged
in
amino
acid
sequence
for
a
year/
decade
or
longer?

6.
EPA
is
trying
to
judge
whether
a
scientifically
appropriate
level
of
maximum
permissible
overall
amino
acid
sequence
variation
could
be
determined
when
identifying
a
specific
enzyme.

a.
What
types
of
differences
may
exist
among
enzyme
variants
that
differ
by
a
single
amino
acid
change?
that
differ
in
amino
acid
composition
by
0.5%?
1%?
10%?
etc.?

b.
How
much
does
the
region
of
the
enzyme
in
which
the
variation
occurs
matter?
For
example,
how
important
are
changes
in
the
amino
acid
sequence
of
the
active
site
versus
the
rest
of
the
molecule?
Are
there
other
regions
of
the
enzyme
that
are
considered
important,
i.
e.,
where
sequence
is
generally
conserved?

d.
How
important
are
deletions
and/
or
excisions
in
determining
differences
between
enzymes?

e.
How
easy
would
it
be
for
a
typical
enzyme
manufacturer
to
determine
the
location
of
the
active
site
or
other
specific
regions
mentioned
in
6b?


3:
00
PM
BREAK

3:
15
PM
Panel
Discussion
(
continued)

7.
EPA
wants
to
assess
the
efficacy
of
existing
sequencing
technologies.

a.
How
accurate
and
reproducible
are
readily
available
amino
acid
sequencing
techniques
and
instrumentation?
Page
4
of
8
b.
How
accurate
and
reproducible
are
readily
available
nucleotide
sequencing
techniques
and
instrumentation?

c.
Does
the
accuracy
of
the
result
depend
on
the
choice
of
method?

d.
How
rapidly
are
sequencing
techniques
improving
or
new
techniques
being
developed?

e.
How
reliably
can
one
predict
the
amino
acid
sequence
of
the
final
gene
product
based
on
the
nucleotide
sequence?

8.
What
additional
information
would
be
gained,
if
any,
by
a
more
detailed
structural
description
that
included
in
addition
to
amino
acid
sequence:

a.
glycosylation
sites
(
and
the
composition
of
these
carbohydrate
moieties),

b.
coenzymes
(
prosthetic
groups),

c.
cofactors,
and/
or
d.
other
post­
translational
modifications
to
residues
of
the
amino
acid
chain?


4:
30
PM
ADJOURNMENT
Page
5
of
8
FIFRA
SCIENTIFIC
ADVISORY
PANEL
(
SAP)
OPEN
MEETING
MAY
4,
2005
FIFRA
SAP
WEB
SITE
http://
www.
epa.
gov/
scipoly/
sap/
OPP
Docket
Telephone:
(
703)
305­
5805
Docket
Number:
OPP­
2005­
0060
TSCA
INVENTORY
NOMENCLATURE
FOR
ENZYMES
AND
PROTEINS
WEDNESDAY,
MAY
4,
2005
Holiday
Inn
 
Rosslyn
at
Key
Bridge
1900
North
Fort
Myer
Drive
Arlington,
Virginia
22209
Telephone:
(
703)
807­
2000

8:
30
AM
Introduction
and
Identification
of
Panel
Members
 
Steven
Heeringa,
Ph.
D.
(
FIFRA
SAP
Session
Chair)


8:
35
AM
Administrative
procedures
by
Designated
Federal
Official
 
Paul
Lewis,
PhD.


8:
40
AM
Follow­
up
from
Previous
Day's
Discussion
­
Mark
Segal,
Ph.
D.
(
Risk
Assessment
Division,
Office
of
Pollution
Prevention
and
Toxics,
EPA)


9:
00
AM
Panel
Discussion
(
continued)

Source
The
SOURCE
of
an
enzyme
refers
to
(
1)
the
organism
from
which
the
gene
encoding
the
enzyme
was
derived,
i.
e.,
the
original
source
and
(
2)
the
organism
or
manufacturing
platform
(
e.
g.,
tissue
culture)
in
which
the
enzyme
is
produced,
i.
e.,
the
production
source.
In
the
questions
below,
please
consider
what
scientific
support
there
is
for
using
source
information
to
differentiate
among
enzymes
and
what
level
of
detail
would
be
scientifically
appropriate
for
this
purpose.

9.
What
information
about
an
enzyme's
structure
could
be
gained
by
knowing
a.
the
original
source
of
the
enzyme?

b.
the
production
source
of
the
enzyme?

10.
If
original
source
information
were
used
as
an
identification
element
to
discriminate
among
enzymes,
what
level
of
taxonomic
specificity
(
e.
g.,
family,
genus,
species,
subspecies,
population,
biovar,
culture
line)
would
be
most
scientifically
appropriate
to
use
for
each
of
the
following
categories?
What
if
production
source
information
were
used?
(
Note:
EPA
recognizes
that
taxonomic
revisions
may
change
the
names
of
particular
organisms
and
can
utilize
mechanisms
for
normalizing
organism
nomenclature,
but
that
consideration
does
not
need
to
be
addressed
by
the
panel.)

a.
plants
Page
6
of
8
b.
animals
c.
fungi
d.
bacteria
e.
other
micro­
organisms

10:
30
AM
BREAK
11.
How
could
source
be
described
if
taxonomic
names
were
inappropriate
because
either
the
original
or
production
source
were
artificial?
Examples
of
such
new
technologies
could
include
enzymes
produced/
developed
through
gene
splicing
or
ex
vivo
chemical
synthesis.

12.
What
information
about
an
enzyme's
structure
could
be
gained
by
additional
details
about
source
including:

a.
the
particular
tissue
or
organ
of
a
given
source
organism
from
which
they
were
derived
(
e.
g.,
swine
pancreatic
tissue
vs.
swine
salivary
glands)?

b.
the
chemical,
geographic,
and/
or
environmental
conditions
from
which
source
organisms
were
isolated
(
e.
g.,
soil,
water,
feces,
etc.)?

c.
manipulations
of
the
enzyme

s
original
source
prior
to
gene
transfer
(
e.
g.,
through
rDNA
technology,
radiation
treatment,
altered
rearing
conditions,
etc.)?

d.
manipulations
of
an
enzyme

s
production
source
prior
to
and/
or
following
gene
transfer?

e.
other
relevant
aspects
of
source
that
are
not
mentioned
(
please
specify
what
would
be
of
value).


12:
00
PM
LUNCH

1:
00
PM
Panel
Discussion
(
continued)

Processing
The
PROCESSING
of
an
enzyme
refers
to
procedures
used
to
isolate
the
enzyme
from
the
production
organism
or
manufacturing
platform,
procedures
used
to
purify
the
enzyme,
and/
or
any
chemical
reactions
to
which
the
enzyme
is
subjected
to
produce
the
final
enzyme
product.
In
the
questions
below,
please
consider
what
scientific
support
there
is
for
using
certain
processing
information
to
differentiate
among
enzymes
and
identify
the
level
of
detail
that
would
be
scientifically
appropriate
for
this
purpose.
What
information
about
an
enzyme's
structure
could
be
gained
by
knowing
which
of
certain
processing
techniques
were
used
in
its
production?

13.
What
information
about
an
enzyme's
structure
could
be
gained
by
knowing
which
of
certain
processing
techniques
were
used
in
its
production?
Page
7
of
8
14.
EPA
anticipates
that
certain
processing
techniques
may
be
so
routine
and/
or
chemically
inconsequential
that
their
reporting
would
be
unnecessary,
while
other
processing
techniques
would
have
significant
effects
on
the
chemical
structure
and/
or
properties
of
an
enzyme.
The
Agency
is
trying
to
assess
how
practical
it
would
be
to
create
a
list
of
processing
techniques
that
need
not
be
included
as
part
of
enzyme
identity.

a.
What
processing
techniques
are
used
in
the
isolation
and
purification
of
enzymes?

b.
Which
processing
techniques
could
change
the
chemical
structure
of
the
enzyme?
Which
could
change
chemical
properties
that
would
indicate
an
underlying
structural
change?

c.
Describe
the
chemical
or
structural
changes
expected
to
occur
from
the
use
of
the
processing
techniques
identified
in
14(
b).

d.
Which
processing
techniques
would
not
be
expected
to
cause
any
structural
changes
to
the
enzyme?
Which
would
not
be
expected
to
cause
any
chemical
property
changes?


3:
00
AM
BREAK

3:
15
PM
Panel
Discussion
(
continued)

15.
EPA
is
trying
to
anticipate
whether
inclusion
of
processing
in
enzyme
identity
will
increase
in
importance
as
a
result
of
future
advances
in
enzyme
production.

a.
What
new
processing
techniques
are
being
developed?

b.
How
might
these
techniques
change
an
enzyme's
chemical
structure
or
properties?

How
frequently
are
new
processing
techniques
for
enzymes
adopted?

Other/
General
Questions:

16.
Aside
from
function,
sequence,
source,
and
processing,
are
any
other
data
elements
crucial
for
enzyme
identification?

17.
Are
there
any
special
considerations
that
should
be
taken
into
account
when
identifying
enzymes
with
multiple,
non­
identical
subunits?
For
example,
a.
when
only
one
subunit
is
modified?
b.
when
a
modified
enzyme
is
a
component
of
an
enzyme
complex?
c.
when
a
multi­
functional,
multi­
component
enzyme
performs
a
sequence
of
reactions?
d.
when
an
enzyme
has
another
non­
catalytic
function,
e.
g.,
a
binding
site?
e.
under
any
other
circumstances?

18.
Although
EPA
believes
that
all
four
identification
elements
are
critical
for
enzyme
identification
for
TSCA
purposes,
the
Agency
is
trying
to
judge
their
relative
importance.
a.
Do
any
data
elements
warrant
greater
emphasis
than
others
because
differences
in
those
data
element(
s)
reflect
more
significant
differences
in
an
enzyme's
physical
and/
or
chemical
properties
than
the
others
do?

b.
If
data
for
sequence,
source,
and
processing
were
the
same
for
two
enzymes
(
at
the
level
of
detail
you
have
determined
to
be
appropriate
in
the
questions
above),
what
Page
8
of
8
additional
information
about
chemical
structure
and/
or
properties
would
be
provided
by
distinguishing
the
enzymes
based
on
function?

c.
If
data
for
function,
sequence,
and
processing
were
the
same
for
two
enzymes
(
at
the
level
of
detail
you
have
determined
to
be
appropriate
in
the
questions
above),
what
additional
information
about
chemical
structure
and/
or
properties
would
be
provided
by
distinguishing
the
enzymes
based
on
original
source?
production
source?

d.
If
data
for
function,
sequence,
and
source
were
the
same
for
two
enzymes
(
at
the
level
of
detail
you
have
determined
to
be
appropriate
in
the
questions
above),
what
additional
information
about
chemical
structure
and/
or
properties
would
be
provided
by
distinguishing
the
enzymes
based
on
processing?


5:
00
PM
ADJOURNMENT
Please
be
advised
that
agenda
times
are
approximate.
For
further
information,
please
contact
the
Designated
Federal
Official
for
this
meeting,
Paul
Lewis
via
telephone:
(
202)
564­
8450;
fax:
(
202)
564­
8382;
or
email:
lewis.
paul@
epa.
gov
